BACKGROUND

Coronary heart disease is the leading cause of mortality worldwide. A high-fat diet, rich in saturated fatty acids and low in polyunsaturated fatty acids, is said to be an important cause of atherosclerosis and cardiovascular diseases.

METHODS

In this experimental study, 40 male rabbits were randomly assigned to eight groups of five to receive normal diet, hypercholesterolemic diet, normal diet plus ghee, normal diet plus olive oil, normal diet plus hydrogenated oil, hypercholesterolemic diet plus ghee, hypercholesterolemic diet plus olive oil, and hypercholesterolemic diet plus hydrogenated oil. They received rabbit chow for a period of 12 weeks. At the start and end of the study, fasting blood samples were taken from all animals to measure biochemical factors including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), fasting blood sugar (FBS), and C-reactive protein (CRP). Moreover, aorta, left and right coronary arteries were dissected at the end of the study to investigate fatty streak formation (FSF). Data was analyzed in SPSS at a significance level of 0.05.

RESULTS

In rabbits under normal diet, ghee significantly increased TC, LDL, and HDL compared to the beginning (P < 0.01) and also to the other two types of fat (P < 0.05). Moreover, normal diet plus olive oil significantly enhanced FSF in left coronary arteries and aorta compared to normal diet plus ghee. In groups receiving hypercholesterolemic diets, ghee significantly increased HDL and CRP (P < 0.05) and significantly decreased FBS (P < 0.01). The hypecholesterolemic diet plus olive oil significantly increased HDL (P < 0.01). Supplementation of hypecholesterolemic diet with ghee significantly increased HDL and FBS in comparison with hydrogenated oil. Significant increase of FBS was also detected with the use of ghee compared to olive oil. Ghee also significantly reduced FSF in left and right coronary arteries compared to olive oil. FSF in left coronary arteries was significantly lower in the hypecholesterolemic diet plus ghee group compared to the hypecholesterolemic diet plus hydrogenated oil group.

CONCLUSION

According to the achieved results, future clinical trial studies and investigation of other risk factors such as inflammatory factors are required.

Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4×10−8), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6×10−8). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4×10−2 for rs11656696 and p = 9.1×10−4 for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

Author Summary

Glaucoma is a major eye disease in the elderly and is the second leading cause of blindness worldwide. The numerous familial glaucoma cases, as well as evidence from epidemiological and twin studies, strongly support a genetic component in developing glaucoma. However, it has proven difficult to identify the specific genes involved. Intraocular pressure (IOP) is the major risk factor for glaucoma and the only target for the current glaucoma therapy. IOP has been shown to be highly heritable. We investigated the role of common genetic variants in IOP by performing a genome-wide association study. Discovery analyses in 11,972 participants and subsequent replication analyses in a further 7,482 participants yielded two common genetic variants that were associated with IOP. The first (rs11656696) is located in GAS7 at chromosome 17, the second (rs7555523) in TMCO1 at chromosome 1. Both variants were associated with glaucoma in a meta-analysis of 4 case-control studies. GAS7 and TMCO1 are expressed in the ocular tissues that are involved in glaucoma. Both genes functionally interact with the known glaucoma disease genes. These data suggest that we have identified two genes involved in IOP regulation and glaucomatous neuropathy.

The present study was aimed at investigating the awareness level about warning signs of cancer and its determinants in an Iranian general population. This cross-sectional interview-based survey investigated 2,500 people aged 18 years and over, as a representative sample of Tehran population. Latent class regression was applied for analyzing data. A small (18.8%) proportion of the respondents had high level of knowledge, and 54.5% had moderate awareness, and 26.7% had low level of awareness. Most effective predictors for awareness were educational attainment, sex, and marital status. The findings suggest that the overall level of knowledge about warning signs of cancer among the public is low, particularly about some specific signs. Accordingly, educational and intervention programmes, with special attention placed on particular at-risk populations, to increase awareness about the disease leading to its early diagnosis are needed.

Background

Elevated serum soluble E-selectin levels have been associated with a number of diseases. Although E-selectin levels are heritable, little is known about the specific genetic factors involved. E-selectin levels have been associated with the ABO blood group phenotype.

Methods and Results

We performed a high-resolution genome-wide association study of serum soluble E-selectin levels in 685 white individuals with type 1 diabetes from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study to identify major loci influencing levels. Highly significant evidence for association (P=10−29) was observed for rs579459 near the ABO blood group gene, accounting for 19% of the variance in E-selectin levels. Levels of E-selectin were higher in O/O than O/A heterozygotes, which were likewise higher than A/A genotypes. Analysis of subgroups of A alleles reveals heterogeneity in the association, and even after this was accounted for, an intron 1 SNP remained significantly associated. We replicate the ABO association in nondiabetic individuals.

Conclusion

ABO is a major locus for serum soluble E-selectin levels. We excluded population stratification, fine-mapped the association to sub-A alleles, and also document association with additional variation in the ABO region.

OBJECTIVE

Glycemia is a major risk factor for the development of long-term complications in type 1 diabetes; however, no specific genetic loci have been identified for glycemic control in individuals with type 1 diabetes. To identify such loci in type 1 diabetes, we analyzed longitudinal repeated measures of A1C from the Diabetes Control and Complications Trial.

RESEARCH DESIGN AND METHODS

We performed a genome-wide association study using the mean of quarterly A1C values measured over 6.5 years, separately in the conventional (n = 667) and intensive (n = 637) treatment groups of the DCCT. At loci of interest, linear mixed models were used to take advantage of all the repeated measures. We then assessed the association of these loci with capillary glucose and repeated measures of multiple complications of diabetes.

RESULTS

We identified a major locus for A1C levels in the conventional treatment group near SORCS1 (10q25.1, P = 7 × 10−10), which was also associated with mean glucose (P = 2 × 10−5). This was confirmed using A1C in the intensive treatment group (P = 0.01). Other loci achieved evidence close to genome-wide significance: 14q32.13 (GSC) and 9p22 (BNC2) in the combined treatment groups and 15q21.3 (WDR72) in the intensive group. Further, these loci gave evidence for association with diabetic complications, specifically SORCS1 with hypoglycemia and BNC2 with renal and retinal complications. We replicated the SORCS1 association in Genetics of Diabetes in Kidneys (GoKinD) study control subjects (P = 0.01) and the BNC2 association with A1C in nondiabetic individuals.

CONCLUSIONS

A major locus for A1C and glucose in individuals with diabetes is near SORCS1. This may influence the design and analysis of genetic studies attempting to identify risk factors for long-term diabetic complications.

Objectives:

This study was conducted to explore the barriers to physical activity in a representative sample of Iranian children and adolescents.

Methods:

The study was conducted in 2007 in urban and rural areas of Isfahan district in Iran. In the qualitative part, we used the grounded theory approach, including semi-structured focus group discussions and indepth interviews. The quantitative part comprised 600 randomly selected students.

Results:

The qualitative study included 34 school students (16 girls), 20 parents (11 mothers) and 11 school staff. All students disclosed that studying was a priority. They pointed to lack of safe and easy-access place for physical activity and unsupportive family as the main barriers. Lack of self-confidence and low selfworth were the two other concepts developed in this context. Parents pointed to lack of safe and easy-access place for activity followed by the priority of studying. The concepts derived from interviews with school staff included unhealthy modeling of parents, priority of studying, and inadequate public knowledge about how to integrate physical activity in routine daily life. The quantitative survey comprised 600 students including 286 (47.8%) girls. Parents’ education level had inverse association with children’s physical activity level. Significant inverse associations of self-efficacy and physical activity levels were documented.

Conclusions:

Increasing the public knowledge about adopting physical activity habits in routine daily life, informing the families and students about the benefits of physical activity to improve learning, as well as providing safe places such as using the school facilities in non-school hours should be considered in planning effective preventive strategies and interventions.

Purpose

Posterior polymorphous corneal dystrophy (PPCD) is a genetically heterogeneous autosomal dominant condition which maps to the pericentromeric region of chromosome 20. Mutations in the VSX1 transcription factor have been reported in patients affected with PPCD, keratoconus, or a combination of both phenotypes. However, no mutation was identified in the coding region of VSX1 in the family used for the original mapping. To clarify the genetic basis of PPCD1, a thorough analysis was performed on the original PPCD1 family and two other PPCD1-linked families. As part of the analysis, the expression profile, transcript variants, and evolutionary conserved regions of VSX1, a key candidate gene within the linkage interval, were characterized.

Methods

Haplotype analysis was performed using highly informative markers on the pericentromeric region of chromosome 20. VSX1 transcript variants were identified using RT–PCR and characterized by 3′RACE assay. Temporal expression profile of VSX1 was evaluated using semi-quantitative real-time RT–PCR on human tissues. Evolutionary conserved regions (ECRs) were identified in the vicinity of VSX1 using publicly available sequence alignments (UCSC and rVista) and sequenced for mutation analysis.

Results

Recombination events were identified that narrow the PPCD1-disease interval from 20 to 16.44 cM. This smaller interval includes the CHED1 locus and a recently described PPCD locus in Czech families. The three strongest candidate genes of the PPCD1-CHED1 overlap region (RBBP9, ZNF133, SLC24A3) did not show any mutations in our PPCD1-linked families. Semi-quantitative real-time RT–PCR detected VSX1 expression in neonatal human cornea. Six transcript variants of VSX1 were characterized. Four of the transcript variants spliced to two novel exons downstream of the gene. Mutation analysis of the PPCD1-linked families did not reveal any mutations in the full genomic sequence of VSX1 (considering all splice variants) or in the six cis- regulatory modules predicted in the vicinity of VSX1 (100 kb).

Conclusions

This is the first documentation of VSX1 expression in human neonatal cornea. We provide evidence for genetic heterogeneity of chromosome 20-related PPCD and refinement of the original PPCD1 interval. The full genomic sequence of VSX1 and coding exons of three other candidate genes were excluded from being pathogenic in the original PPCD1 family.