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1.  Lack of Association Between Dopamine Beta-Hydroxylase (DBH) 19-bp Insertion/Deletion Polymorphism and Risk of Schizophrenia  
Iranian Journal of Psychiatry  2016;11(4):239-243.
Objective: Interaction between genetic and environmental factors is considered as major factors in Schizophrenia (SCZ). It has been shown that dopaminergic and noradrenergic neurotransmission dysfunction play an essential role in the SCZ pathogenesis.
This study aimed to find the impact of functional 19-bp insertion/deletion (ins/del) polymorphism in dopamine beta-hydroxylase (DBH) gene on SCZ risk in a sample of Iranian population.
Method: This case-control study was conducted on 109 SCZ patients and 116 matched healthy subjects. Genomic DNA samples were extracted from peripheral blood cells using salting out method. Genotyping of 19-bp ins/del DBH polymorphism was done using Polymerase Chain Reaction (PCR) method.
Results: Neither the overall chi-square comparison of cases and controls (𝜒2 = 0.56, p = 0.756), nor the logistic regression analysis (which was computed in codominant, dominant and recessive model of inheritance) showed any association between DBH 19-bp I/D and SCZ in a sample of southeast Iranian population.
Conclusion: Overall, our results did not support an association between DBH 19-bp I/D polymorphism and risk/protection of SCZ.
PMCID: PMC5206326  PMID: 28050184
Deletion; Dopamine Beta-Hydroxylase; Insertion; Polymorphism; Schizophrenia
2.  Evaluation of interferon-induced transmembrane protein-3 (IFITM3) rs7478728 and rs3888188 polymorphisms and the risk of pulmonary tuberculosis 
Biomedical Reports  2016;5(5):634-638.
The current study aimed to examine the possible association between the interferon-induced transmembrane protein-3 (IFITM3) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample population. This case-control study was conducted on 188 PTB patients and 169 healthy subjects. The rs7478728 and rs3888188 variants of IFITM3 were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The findings showed no significant association between rs7478728 polymorphism and risk of PTB. Regarding rs3888188 polymorphism, the TG genotype as well as G allele significantly increased the risk of PTB [odds ratio (OR)=2.48, 95% confidence interval (CI): 1.42–4.53; P=0.002, and OR=2.26, 95% CI: 1.33–3.86; P=0.003, respectively]. In conclusion, the findings revealed that rs3888188 polymorphism increased the risk of PTB in a sample of Iranian population. Additional investigation with larger sample sizes and different ethnicities are needed to verify our findings.
PMCID: PMC5103685  PMID: 27882230
tuberculosis; IFITM3; polymorphism
3.  Evaluation of HLA-G 14 bp Ins/Del and +3142G>C Polymorphism with Susceptibility and Early Disease Activity in Rheumatoid Arthritis 
Advances in Medicine  2016;2016:4985745.
Purpose/Background. Mounting evidence designates that HLA-G plays a role in the regulation of inflammatory processes and autoimmune diseases. There are controversial reports concerning the impact of HLA-G gene polymorphism on rheumatoid arthritis (RA). This study was aimed at examining the impact of 14 bp ins/del and +3142G>C polymorphism with susceptibility and early disease activity in RA patients in a sample of the Iranian population. Methods. This case-control study was done on 194 patients with RA and 158 healthy subjects. The HLA-G rs1063320 (+3142G>C) and rs66554220 (14 bp ins/del) variants were genotype by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFP) and PCR method, respectively. Results. The HLA-G +3142G>C polymorphism significantly decreased the risk of RA in codominant (OR = 0.61, 95% CI = 0.38–0.97, p = 0.038, GC versus GG; OR = 0.36, 95% CI = 0.14–0.92, p = 0.034, CC versus GG), dominant (OR = 0.56, 95% CI = 0.36–0.87, p = 0.011, GC + CC versus GG), and allele (OR = 0.58, 95% CI = 0.41–0.84, p = 0.004, C versus G) inheritance models tested. Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. In addition, no significant association was found between the polymorphism and early disease activity. Conclusion. In summary, our results showed that HLA-G +3142G>C gene polymorphism significantly decreased the risk of RA in a sample of the Iranian population.
PMCID: PMC5004028  PMID: 27610404
4.  FEN1 −69G>A and +4150G>T polymorphisms and breast cancer risk 
Biomedical Reports  2016;5(4):455-460.
Flap endonuclease 1 (FEN1), a DNA repair protein, is important in preventing carcinogenesis. Two functional germ line variants −69G>A (rs174538) and +4150G>T (rs4246215) in the FEN1 gene have been associated with risk of various types of cancer. The aim of the present study was to evaluate the possible impact of FEN1 polymorphisms on risk of breast cancer (BC) in a sample of Iranian subjects. The FEN1 −69G>A and +4150G>T polymorphisms were analyzed in a case-control study that included 266 BC patients and 225 healthy females. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to genotype the variants. The findings demonstrated that the FEN1 −69G>A and +4150G>T polymorphisms were not associated with BC risk in co-dominant, dominant and recessive inheritance models. The findings indicated that GG/GT, GA/GG and GA/TT genotypes significantly decreased the risk of BC when compared with −69GG/+4150GG. Furthermore, haplotype analysis indicated that −69G/+4150T as well as −69A/+4150G significantly decreased the risk of BC compared with −69G/+4150G. Thus, these findings demonstrated that haplotypes of FEN1 −69G>A and +4150G>T polymorphisms decreased the risk of BC in an Iranian population. Further studies with larger sample sizes and different ethnicities are required to validate the present findings.
PMCID: PMC5038467  PMID: 27699013
flap endonuclease 1; breast cancer; polymorphism
5.  Association Between Vascular Endothelial Growth Factor Gene Polymorphisms with Breast Cancer Risk in an Iranian Population 
Breast cancer (BC) is one of the most causes of death in women worldwide. It affects Iranian female population approximately a decade earlier than those in other parts of the world. Previous studies have shown that vascular endothelial growth factor (VEGF) gene variants were associated with BC risk. The current study aimed to evaluate the impact of VEGF rs3025039 (+936C>T), rs2010963 (+405C>G), rs833061 (-460T>C), rs699947 (-2578C>A), and rs35569394 (18-bp I/D) polymorphisms on BC risk in an Iranian population in southeast of Iran. This case–control study was done on 250 BC patients and 215 healthy women. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or PCR was used to genotype the polymorphisms. Our findings showed that VEGF rs699947 variant increased the risk of BC (OR = 1.71, 95% CI = 1.15–2.54, P = 0.009, CA vs CC; OR = 2.12, 95% CI = 1.14–3.93, P = 0.021, AA vs CC; OR = 1.78, 95% CI = 1.22–2.60, P = 0.004, CA+AA vs CC; OR = 1.47, 95% CI = 1.12–1.92, P = 0.005, A vs C). The VEGF rs3025039, rs2010963, rs833061, and rs35569394 variants were not associated with risk/protection of BC. In conclusion, our results proposed that VEGF rs699947 polymorphism may increase the risk of BC development. Furthers studies with larger sample sizes and different ethnicities are necessary to confirm our findings.
PMCID: PMC4933538  PMID: 27398026
vascular endothelial growth factor; VEGF; breast cancer; polymorphism
6.  Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population 
Background: The present study was aimed to examine the possible association between methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population.
Subjects and Methods: A total of 220 subjects including 100 children diagnosed with ALL and 120 healthy children participated in the case-control study. The single nucleotide polymorphisms (SNPs) of MTHFR were determined by ARMS-PCR or PCR-RFLP method.
Results: Our investigation revealed that rs13306561 both TC and TC + CC genotypes decreased the risk of ALL compared to TT genotype (OR=0.32, 95%CI=0.15-0.68, p=0.002 and OR=0.35, 95%CI=0.17-0.70, p=0.003, respectively). In addition, the rs13306561 C allele decreased the risk of ALL in comparison with T allele (OR=0.42, 95% CI=0.22-0.78, P=0.005). MTHFR rs1801131 (A1298C) polymorphism showed that the AC heterozygous genotype decreased the risk of ALL in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037). Neither the overall Chi-square comparison of cases and control subjects (𝜒2=5.54, p=0.063) nor the logistic regression analysis showed significant association between C677T polymorphism and ALL (OR=1.25, 95% CI=0.69-2.23, p=0.552; CT vs. CC).
Conclusion: The current investigation findings showed that MTHFR rs1801131 and rs13306561 polymorphisms decreased the risk of ALL in the population which has been studied. Further studies with larger sample sizes and different ethnicities are required to validate our findings.
PMCID: PMC4969557  PMID: 27489588
MTHFR; Polymorphism; Acute lymphocytic leukemia
7.  Study of Genetic Variation of Leishmania major Based on Internal Transcribed Spacer 1 (ITS1) in Chabahar, Iran 
Zoonotic cutaneous leishmaniasis (ZCL) is polymorphic disease that may show various clinical manifestations.
This study investigates the determination of genetic variation within the species of Leishmania major isolates from new cases in Chabahar, a port city in Southeast Iran (situated at the Iran-Pakistan border). Migration in this region indicates that leishmaniasis is spreading gradually, and a new micro-habitat focus appears each year.
Materials and Methods
A variety of nucleic acid detection methods that target both DNA and RNA have been developed. The restriction fragment length polymorphism analysis of amplified internal transcribed spacer 1 with polymerase chain reaction (ITS1-RFLP PCR) assay is a multipurpose tool for the diagnosis of Leishmania from clinical samples and for enabling the determination of the infecting Leishmania species. The goal of this study was the identification of species based on ITS1-RFLP in the ribosomal operon of L. major from clinically different forms of ZCL amplified by PCR, followed by the digestion of the PCR product with restriction enzymes. The profiles were observed and visualized in agarose gel under UV light. We used direct smears to identify the parasites. While taking the smear, samples were collected for culture or direct PCR. We used the PCR-RFLP assay of the ITS1 genes for direct identification of Leishmania species in 24 out of 33 suspected patients. PCR-ITS1 amplification was done on the 24 samples confirmed by culture via growth and parasitological methods.
Of the 24 isolates, 21 had 350 bp bands (87.5%) and three had 450 bp bands (12.5%). After using the restriction enzyme, banding patterns including fragments of 210 and 140 bp for L. major were detected in 19 cases.
The L. major species causing ZCL in Chabahar have limited genetic variation. There seems to be little manifestation of diversity between these lesions as a new focus of disease, and new micro-habitats for the disease are appearing in parts of this region.
PMCID: PMC5013237  PMID: 27635211
Cutaneous Leishmaniasis; ITS1, PCR-RFLP; Genetic Variation
8.  Evaluation of the pri-miR-34b/c rs4938723 polymorphism and its association with breast cancer risk 
Biomedical Reports  2016;5(1):125-129.
MicroRNAs (miRNAs or miRs) are a family of small non-coding RNAs that function as oncogenes or tumor suppressor genes. Recent evidence suggests that the pri-miR-34b/c rs4938723 variant is associated with the development of cancer. At present, there is an inconsistent association between the single-nucleotide polymorphism in pri-miR-34b/c and cancer in the limited studies. The present study is a case-control investigation, with 263 breast cancer (BC) patients and 221 control women, which examined the potential association of the pri-miR-34b/c rs4938723 polymorphisms with BC susceptibility. The polymorphisms were genotyped by the polymerase chain reaction restriction fragment length polymorphism method. No significant association between the pri-miR-34b/c rs4938723 variant and BC was identified [TC vs. TT: Odds ratio (OR), 0.87; 95% confidence interval (CI), 0.60–1.26; P=0.506; CC vs. TT: OR, 1.22; 95% CI, 0.61–2.47; P=0.600; TC+CC vs. TT: OR, 0.91; 95% CI, 0.64–1.31; P=0.648; CC vs. TT+TC: OR, 1.32; 95% CI, 0.67–2.59; P=0.498; C vs. T: OR, 0.99; 95% CI, 0.75–1.31; P=0.986]. However, a significant association was observed between the pri-miR-34b/c rs4938723 genotypes and clinicopathological characteristics, such a grade, progesterone receptor and human epidermal growth factor receptor 2 status were observed (P<0.05). These findings suggest that the pri-miR-34b/c rs4938723 variant may not be a risk factor for the development of BC.
PMCID: PMC4906800  PMID: 27347415
pri-miR-34b/c; breast cancer; polymorphism
9.  Evaluation of Antidiabetic and Antihyperlipidemic Effects of Peganum harmala Seeds in Diabetic Rats 
Cholesterol  2016;2016:7389864.
The present study was carried out to investigate the antidiabetic and antihyperlipidemic properties of hydroalcoholic extract of Peganum harmala in streptozotocin-induced diabetic male rats. In an experimental study, 64 normal Wistar albino male rats (200–230 g) were randomly divided into 8 groups. Control and diabetic rats were treated with normal saline and three different doses (30, 60, and 120 mg/kg) of hydroalcoholic extract of Peganum harmala seeds for 4 weeks orally. At the end of treatment, blood samples were taken and glucose, triglycerides, total cholesterol, LDL-c, HDL-c, malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, GGT, bilirubin, and glycosylated hemoglobin (HbA1C) were determined. STZ-induced diabetic rats showed significant changes in the values of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C in comparison with normal rats. Administration of the extract to diabetic rats resulted in a remarkable decrease in glucose, lipid profiles, MDA, ALT, AST, GGT, bilirubin, and HbA1C levels and increase in TAC relative to diabetic group. The results of this study indicated that hydroalcoholic extract of Peganum harmala seeds possesses antidiabetic and hypolipidemic activities and could be useful in treatment of diabetes.
PMCID: PMC4848417  PMID: 27190643
10.  Promoter Methylation and mRNA Expression of Response Gene to Complement 32 in Breast Carcinoma 
Journal of Cancer Epidemiology  2016;2016:7680523.
Background. Response gene to complement 32 (RGC32), induced by activation of complements, has been characterized as a cell cycle regulator; however, its role in carcinogenesis is still controversial. In the present study we compared RGC32 promoter methylation patterns and mRNA expression in breast cancerous tissues and adjacent normal tissues. Materials and Methods. Sixty-three breast cancer tissues and 63 adjacent nonneoplastic tissues were included in our study. Design. Nested methylation-specific polymerase chain reaction (Nested-MSP) and quantitative PCR (qPCR) were used to determine RGC32 promoter methylation status and its mRNA expression levels, respectively. Results. RGC32 methylation pattern was not different between breast cancerous tissue and adjacent nonneoplastic tissue (OR = 2.30, 95% CI = 0.95–5.54). However, qPCR analysis displayed higher levels of RGC32 mRNA in breast cancerous tissues than in noncancerous tissues (1.073 versus 0.959; P = 0.001), irrespective of the promoter methylation status. The expression levels and promoter methylation of RGC32 were not correlated with any of patients' clinical characteristics (P > 0.05). Conclusion. Our findings confirmed upregulation of RGC32 in breast cancerous tumors, but it was not associated with promoter methylation patterns.
PMCID: PMC4828546  PMID: 27118972
11.  Association between single nucleotide polymorphism in miR-499, miR-196a2, miR-146a and miR-149 and prostate cancer risk in a sample of Iranian population 
Journal of Advanced Research  2016;7(3):491-498.
Graphical abstract
MicroRNAs (miRNAs) play an important role in regulating gene expression at the post-transcriptional level and are involved in numerous physiological processes. Accumulating evidence suggests that single-nucleotide polymorphisms (SNPs) in human miRNA genes may affect miRNA biogenesis pathway and influence the susceptibility to several diseases such as cancer. The present study aimed to evaluate the impact of miR-499 rs3746444, miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms on prostate cancer (PCa) risk in a sample of Iranian population. This case-control study was done on 169 patients with pathologically confirmed PCa and 182 benign prostatic hyperplasia (BPH). The genotyping assays were done using T-ARMS-PCR or PCR-RFLP methods. The findings indicated that CC genotype of miR-499 rs3746444 polymorphism increased the risk of PCa (OR = 1.76, 95% CI = 1.12–2.79, P = 0.019) compared to TT genotype. No statistically significant association was found between miR-196a2 rs11614913, miR-149 rs2292832, and miR-146a rs2910164 polymorphisms and PCa risk. In summary, the findings indicated that miR-499 rs3746444 polymorphism increased the risk of PCa in an Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify the findings of the present study.
PMCID: PMC4856822  PMID: 27222754
Prostate cancer; miR-499; miR-196a2; miR-146a; miR-149; Polymorphism
12.  The Correlation Between Interferon Lambda 3 Gene Polymorphisms and Susceptibility to Hepatitis B Virus Infection 
Hepatitis Monthly  2016;16(3):e34266.
Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection.
This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients.
Patients and Methods
In this case-control study, we determined IFNL3 single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) in 221 individuals, with chronic HBV infection, and 200 healthy individuals, who were voluntary blood donors, with negative test for HBV. Alleles and genotypes analyses were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods.
The frequencies of the rs12979860 and rs8099917 genotypes were not significantly different between the HBV-infected and the control groups (CC:CT:TT of 30.3%:48.0%:21.7% vs. 33.0%:49.0%:18.0%, P > 0.05, and GG:GT:TT of 5.8%:39.4%:54.8% vs. 5.0%:41.0%:54.0%, P > 0.05, respectively). Also, the frequencies of the alleles were not significantly different between both groups (C:T of 54.3%:45.7% vs. 57.5%:42.5%, P > 0.05, and G:T of 25.6%:74.4% vs. 25.5%:74.5%, P > 0.05, respectively) and the chronic HBV infection. There were no significant differences between patients, with at least one rs12979860C and or rs8099917T alleles compared to the healthy controls (rs12979860: CT + CC:TT, OR = 1.26, 95%CI = 0.78 - 2.04, P = 0.341 and rs8099917: GT + TT:GG, OR = 1.03, 95%CI = 0.70 - 1.51, P = 0.877, respectively).
Our study showed no correlation between rs12979860 and rs8099917 SNPs and chronic HBV infection. Further studies, with larger sample sizes and different ethnicities, are necessary to validate our findings.
PMCID: PMC4875561  PMID: 27226800
Genetic Polymorphism; Chronic Hepatitis B; Interferon Lambda 3 (IFNL3)
13.  Estimation of volume density of interdental papilla components in patients with chronic periodontitis and interleukin-6 (-174G/C) gene polymorphisms 
Dental Research Journal  2016;13(2):139-144.
The association between interleukin-6 (IL-6) (-174G/C) gene polymorphisms and level of tissue breakdown and periodontal disease progression is unknown. The present study investigated quantitative parameters of interdental papilla in chronic periodontitis (CP) patients with IL-6 (-174G/C) gene polymorphisms.
Materials and Methods:
Sixty gingival samples were studied. After determination of IL-6 (-174G/C) gene polymorphisms using a tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) technique, 45 gingival tissue samples of CP patients (GG and GC+CC genotypes) were considered as case groups. Fifteen control samples were also collected from healthy individuals. After tissue processing, interdental gingival tissues were exhaustively sectioned into 4 μm-thick sections. Ten to thirteen sections were sampled by systematic uniform random sampling and stained with Masson trichrome, and the volume density (Vv) of the gingival components was estimated using Cavalier's point counting method. Statistical analysis was performed by Student t-test to compare differences between groups. The significance level was set at P < 0.05.
There were statistically significant differences in the Vv of epithelium, connective tissue, collagenous and non-collagenous matrix, and blood vessels between the control and CP groups (P < 0.0001). There were no statistically significant differences in the Vv of epithelium, connective tissue of gingiva, collagenous and non-collagenous matrix, and blood vessels among GG, GC, and CC genotypes in CP patients (P > 0.05).
Results of the current study showed that there was no association between IL-6 (-174G/C) gene polymorphisms and quantitative parameters of interdental papilla in CP patients.
PMCID: PMC4810911  PMID: 27076828
Chronic periodontitis; genes; gingiva; interleukin-6; polymorphism
14.  Effect of Echinophora platyloba DC. essential oil and lycopene on the stability of pasteurized cream obtained from cow milk 
Veterinary Research Forum  2016;7(2):139-148.
The present study was carried out to enhance shelf life of pasteurized cream using Echinophora platyloba essential oil (EEO) and lycopene. For this purpose, two concentrations of EEO (0.10% and 0.50%) and lycopene (20 and 50 ppm) alone and together as combinations were added in pasteurized creams and analyzed for microbial characteristics, sensorial properties and lipid stability during storage at 4 ˚C and 25 ˚C for 14 days. Results of microbial and chemical analyses of experimental pasteurized creams showed that pasteurized creams treated with combinations of the EEO and lycopene in their higher concentrations had the best microbial and chemical properties and the most stability than control during storage (p < 0.05). Results of sensorial evaluation demonstrated that all treatments had favorable overall acceptability, even though, the best sensorial properties were observed in creams with combinations of EEO and lycopene in their lower concentrations. Therefore, based on the results of the present study, application of EEO and lycopene as natural preservatives is especially recommend in high fat dairy products such as butter and cream.
PMCID: PMC4959342  PMID: 27482359
Echinophora Platyloba; Lycopene; Pasteurized cream; Shelf-life
15.  Association Between IL-10 Gene Promoter Polymorphisms (-592 A/C, -819 T/C, -1082 A/G) and Susceptibility to HBV Infection in an Iranian Population 
Hepatitis Monthly  2016;16(2):e32427.
IL-10 can play a vital role in immune response against HBV. Three biallelic SNPs from the transcription start site control the transcription of the IL-10 gene. An association between susceptibility to HBV and IL-10 polymorphisms has been suggested in patients with HBV infection.
The present study was designed to study the association between polymorphisms in interleukin-10 (-1082 A/G, -819 T/C and -592 A/C) promoter gene and chronic hepatitis B virus (HBV) infection.
Patients and Methods
221 chronically infected patients and 200 healthy control subjects were enrolled in the study. Three biallelic (-1082 A/G, -819 T/C and -592 A/C) polymorphisms in the IL-10 promoter gene were determined by PCR-RFLP method.
Persistent HBV infection was associated with IL-10-1082 AG (P = 0.001) and GG (P = 0.004) genotypes and G (P = 0.000) allele. IL-10-819 T/C and -592 A/C genotype and allele frequencies did not show any correlation with the risk of chronic hepatitis B infection.
These results suggest that polymorphisms in interleukin-10 gene promoter influence clinical outcome of HBV infection and susceptibility to HBV infection.
PMCID: PMC4852092  PMID: 27148384
Chronic Hepatitis B; Interleukin-10; Single Nucleotide Polymorphism
16.  Association between IFN-γ +874A/T and IFN-γR1 (-611A/G, +189T/G, and +95C/T) Gene Polymorphisms and Chronic Periodontitis in a Sample of Iranian Population 
Background. Interferon gamma (IFN-γ) is an immune regulatory cytokine that acts through its receptor and plays important role in progression of inflammatory disease such as chronic periodontitis (CP). The purpose of this study was to determine the differences in the distribution of IFN-γ (+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) gene polymorphisms among CP and healthy individuals and to investigate relationships between these polymorphisms and susceptibility to CP. Materials and Methods. 310 individuals were enrolled in the study including 210 CP patients and 100 healthy controls. Single nucleotide polymorphisms at IFN-γ (+874A/T) and IFN-γR1 (-611A/G, +189T/G, and +95C/T) were analyzed by ARMS-PCR and PCR-RFLP methods. Results. The significant difference was found in genotype and allele frequency of IFN-γ (+874A/T) gene polymorphism in chronic periodontitis patients and healthy controls. The distribution of genotypes and allele frequencies for IFN-γR1 (-611A/G, +189T/G, and +95C/T) were similar among the groups and no differences in the frequencies of alleles or genotypes of IFN-γR1 genetic polymorphisms variants between case and control groups were detected. Conclusion. The finding of this study showed that IFN-γ +874A/T gene polymorphism may affect susceptibility to CP, whereas IFN-γR1 genetic polymorphisms at -611A/G, +189T/G, and +95C/T were not associated with this disease.
PMCID: PMC4707340  PMID: 26823666
17.  Hepatitis B and C virus-induced hepatitis: Apoptosis, autophagy, and unfolded protein response 
World Journal of Gastroenterology  2015;21(47):13225-13239.
AIM: To investigate the co-incidence of apoptosis, autophagy, and unfolded protein response (UPR) in hepatitis B (HBV) and C (HCV) infected hepatocytes.
METHODS: We performed immunofluorescence confocal microscopy on 10 liver biopsies from HBV and HCV patients and tissue microarrays of HBV positive liver samples. We used specific antibodies for LC3β, cleaved caspase-3, BIP (GRP78), and XBP1 to detect autophagy, apoptosis and UPR, respectively. Anti-HCV NS3 and anti-HBs antibodies were also used to confirm infection. We performed triple blind counting of events to determine the co-incidence of autophagy (LC3β punctuate), apoptosis (cleaved caspase-3), and unfolded protein response (GRP78) with HBV and HCV infection in hepatocytes. All statistical analyses were performed using SPSS software for Windows (Version 16 SPSS Inc, Chicago, IL, United States). P-values < 0.05 were considered statistically significant. Statistical analyses were performed with Mann-Whitney test to compare incidence rates for autophagy, apoptosis, and UPR in HBV- and HCV-infected cells and adjacent non-infected cells.
RESULTS: Our results showed that infection of hepatocytes with either HBV and HCV induces significant increase (P < 0.001) in apoptosis (cleavage of caspase-3), autophagy (LC3β punctate), and UPR (increase in GRP78 expression) in the HCV- and HBV-infected cells, as compared to non-infected cells of the same biopsy sections. Our tissue microarray immunohistochemical expression analysis of LC3β in HBVNeg and HBVPos revealed that majority of HBV-infected hepatocytes display strong positive staining for LC3β. Interestingly, although XBP splicing in HBV-infected cells was significantly higher (P < 0.05), our analyses show a slight increase of XBP splicing was in HCV-infected cells (P > 0.05). Furthermore, our evaluation of patients with HBV and HCV infection based on stage and grade of the liver diseases revealed no correlation between these pathological findings and induction of apoptosis, autophagy, and UPR.
CONCLUSION: The results of this study indicate that HCV and HBV infection activates apoptosis, autophagy and UPR, but slightly differently by each virus. Further studies are warranted to elucidate the interconnections between these pathways in relation to pathology of HCV and HBV in the liver tissue.
PMCID: PMC4679754  PMID: 26715805
Cell fate; Cell death; Hepatocyte; Viral infection; Endoplasmic reticulum stress
18.  Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran 
Aim. The present study was undertaken to find out the possible association between interferon-gamma (IFN-γ) receptor 1 (IFNGR1) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Methods. Polymorphisms of IFNGR1 rs1327474 (−611 A/G), rs11914 (+189 T/G), rs7749390 (+95 C/T), and rs137854905 (27-bp ins/del) were determined in 173 PTB patients and 164 healthy subjects. Results. Our findings showed that rs11914 TG genotypes decreased the risk of PTB in comparison with TT (OR = 0.36, 95% CI = 0.21–0.62, and p = 0.0002). The rs11914 G allele decreased the risk of PTB compared with T allele (OR = 0.41, 95% CI = 0.25–0.68, and p = 0.0006). IFNGR1 rs7749390 CT genotype decreased the risk of PTB in comparison with CC genotype (OR = 0.55, 95% CI = 0.32–0.95, and p = 0.038). No significant association was found between IFNGR1 rs1327474 A/G polymorphism and risk/protective of PTB. The rs137854905 (27-bp I/D) variant was not polymorphic in our population. Conclusion. Our findings showed that IFNGR1 rs11914 and rs7749390 variants decreased the risk of PTB susceptibility in our population.
PMCID: PMC4663002  PMID: 26649196
20.  Association of Angiotensin-Converting Enzyme Genotype, Insertion/Deletion Polymorphism and Saphenous Vein Graft Atherosclerosis in Iranian Patients 
The aim of this study was to evaluate possible interactions among Angiotensin-I converting enzyme genotype, insertion/deletion polymorphism and atherosclerosis of vein grafts in Iranian patients, and characterize their clinical and demographic profile.
In this cross-sectional study, patients who underwent coronary artery bypass graft surgery more than five years ago, were included for angiographic analysis. Atherosclerosis was determined by quantitative angiography and adjusted Gensini score. The gene angiotensin converting enzyme I/D polymorphism was detected by polymerase chain reaction.
A total of 102 patients participated in this study. Eighty-four patients were male. The frequency distribution of DD, ID and II polymorphism were 23.6%, 62.7% and 13.7% respectively. There were no differences among genotypic groups in age, sex, number of risk factors, number of vein grafts and months since bypass surgery. According to adjusted Gensini score [0.18±0.12 (II) vs. 0.11±0.09 (ID) and 0.1±0.09 (DD) P=0.021] the II genotype was associated with severity of vein graft atherosclerosis.
Although there are conflicting results about gene angiotensin converting enzyme I/D polymorphism and the degree of venous bypass graft degeneration, this study suggests an association between ACE genotype II and atherosclerosis of saphenous vein grafts, however, large samples considering clinical, demographic and ethnic profile are necessary to confirm these results.
PMCID: PMC4690661  PMID: 26735603
Cardiopulmonary Bypass; Cardiovascular Surgical Procedures; Genetics
21.  Effect of the peels of two Citrus fruits on endothelium function in adolescents with excess weight: A triple-masked randomized trial 
Obesity induces endothelial dysfunction even in the pediatric age group. The possible protective effects of fruits and herbal products on the endothelial dysfunction of obese children remain to be determined. This study aims to investigate the effects of lemon and sour orange peels on endothelial function of adolescents with excess weight.
Materials and Methods:
This triple-masked, randomized placebo-controlled trial was conducted for 1-month among 90 overweight and obese participants, aged 6-18 years. They were randomly assigned into three groups of equal number receiving daily oral capsules containing lemon or sour orange powder or placebo. Flow-mediated dilatation (FMD) was compared between three groups by using analysis of covariance.
Overall, 30 participants in the lemon group, 27 in the sour orange group and 29 in the control group completed the trial. After the trial, mean FMD was significantly (P < 0.001) higher in the lemon group (11.99 ± 4.05) and in the sour orange group (12.79 ± 5.47) than in the placebo group (6.45 ± 2.79). FMD percent change was 145.02 ± 24.34 in the lemon group, 142.04 ± 16.11 in the sour orange group, and 46.73 ± 5.16 in controls (P < 0.001).
This trial showed that consumption of extracts of lemon and sour orange peels, which contain plenty amounts of antioxidants, flavonoids, pectin, and vitamin C, might have significant benefits on endothelial function in children and adolescents with excess weight. Trial registry code: IRCT201311201434N10.
PMCID: PMC4652303  PMID: 26664417
Childhood obesity; endothelial function; Citrus fruits; prevention
22.  Targeting the Mevalonate Cascade as a New Therapeutic Approach in Heart Disease, Cancer and Pulmonary Disease 
Pharmacology & therapeutics  2014;143(1):87-110.
The cholesterol biosynthesis pathway, also known as the mevalonate (MVA) pathway, is an essential cellular pathway that is involved in diverse cell functions. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) is the rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of HMG-CoA to MVA.
Given its role in cholesterol and isoprenoid biosynthesis, the regulation of HMGCR has been intensely investigated. Because all cells require a steady supply of MVA, both the sterol (i.e. cholesterol) and non-sterol (i.e. isoprenoid) products of MVA metabolism exert coordinated feedback regulation on HMGCR through different mechanisms. The proper functioning of HMGCR as the proximal enzyme in the MVA pathway is essential under both normal physiologic conditions and in many diseases given its role in cell cycle pathways and cell proliferation, cholesterol biosynthesis and metabolism, cell cytoskeletal dynamics and stability, cell membrane structure and fluidity, mitochondrial function, proliferation, and cell fate.
The blockbuster statin drugs (‘statins’) directly bind to and inhibit HMGCR, and their use for the past thirty years has revolutionized the treatment of hypercholesterolemia and cardiovascular diseases, in particular coronary heart disease. Initially thought to exert their effects through cholesterol reduction, recent evidence indicates that statins also have pleiotropic immunomodulatory properties independent of cholesterol lowering.
In this review we will focus on the therapeutic applications and mechanisms involved in the MVA cascade including Rho GTPase and Rho kinase (ROCK) signaling, statin inhibition of HMGCR, geranylgeranyltransferase (GGTase) inhibition, and farnesyltransferase (FTase) inhibition in cardiovascular disease, pulmonary diseases (e.g. asthma and chronic obstructive pulmonary disease (COPD), and cancer.
PMCID: PMC4005604  PMID: 24582968
Statins; geranylgeranyl transferase inhibitors; farnesy transferase inhibtors; Rho GTPase; asthma; chronic obstructive pulmonary disease; fibrosis; cancer
23.  Association between Programmed Cell Death 6 Interacting Protein Insertion/Deletion Polymorphism and the Risk of Breast Cancer in a Sample of Iranian Population 
Disease Markers  2015;2015:854621.
It has been suggested that genetic factors contribute to patients' vulnerability to breast cancer (BC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that is known to bind to the products of the PDCD6 gene, which is involved in the apoptosis pathway. The aim of this case-control study is to investigate the relationship between the PDCD6IP 15 bp insertion/deletion (I/D) polymorphism (rs28381975) and BC risk in an Iranian population. A total of 491 females, including 266 BC patients and 225 control subjects without cancer, were enrolled into the study. Our findings revealed that the PDCD6IP 15 bp I/D polymorphism decreased the risk of BC in codominant (OR = 0.44, 95% CI = 0.31–0.65, p < 0.0001, I/D versus DD; OR = 0.39, 95% CI = 0.17–0.88, p = 0.030, I/I versus DD) and dominant (OR = 0.44, 95% CI = 0.30–0.63, p < 0.0001, D/I + I/I versus D/D) tested inheritance models. Also, the PDCD6IP I allele significantly decreased the risk of BC (OR = 0.59, 95% CI = 0.45–0.78, p < 0.001) compared to the D allele.
PMCID: PMC4433669  PMID: 26063962
24.  Evaluation of haptoglobin genotypes in patients with metabolic syndrome: A preliminary report 
ARYA Atherosclerosis  2015;11(3):167-172.
Haptoglobin (Hp) polymorphisms have been suggested to be associated with many pathological conditions, including cardiovascular diseases, infectious diseases, and type 2 diabetes. For the first time, we aimed to investigate the possible association between Hp genotypes and metabolic syndrome (MES) in a sample of Iranian subjects.
In this study, 291 patients with MES according to National Cholesterol Education Program-Adult Treatment Panel III criteria, and 284 healthy individuals have been studied. We determined Hp genotype by polymerase chain reaction.
The frequency of three genotype (Hp1-1, Hp2-1, and Hp2-2) in healthy individuals and patients were 7.74, 39.7, 52.46, and 7.9, 31.61, 60.48 percent, respectively. There was no significant difference between the groups regarding Hp genotypes. The Hp2 allele was the predominant allele in MES (76.29%) and normal subjects (72.54%).
Hp polymorphisms are not risk factor for predisposition to MES in a sample of the Iranian population. Further studies with different ethnicities are required to validate our findings.
PMCID: PMC4568188  PMID: 26405448
Haptoglobin; Phenotype; Metabolic Syndrome
25.  The 19-bp deletion polymorphism of dihydrofolate reductase (DHFR) and nonsyndromic cleft lip with or without cleft palate: evidence for a protective role 
Journal of Applied Oral Science  2015;23(3):272-278.
Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population.
Material and Methods
The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method.
We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P.
Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects.
PMCID: PMC4510661  PMID: 26221921
Dihydrofolate reductase (DHFR); Nonsyndromic cleft lip with or without cleft palate (NS-CL/P); Ins/Del polymorphism

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