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1.  Reliable and rapid characterization of functional FCN2 gene variants reveals diverse geographical patterns 
BMC Medical Genetics  2012;13:37.
Ficolin-2 coded by FCN2 gene is a soluble serum protein and an innate immune recognition element of the complement system. FCN2 gene polymorphisms reveal distinct geographical patterns and are documented to alter serum ficolin levels and modulate disease susceptibility.
We employed a real-time PCR based on Fluorescence Resonance Energy Transfer (FRET) method to genotype four functional SNPs including -986 G > A (#rs3124952), -602 G > A (#rs3124953), -4A > G (#rs17514136) and +6424 G > T (#rs7851696) in the ficolin-2 (FCN2) gene. We characterized the FCN2 variants in individuals representing Brazilian (n = 176), Nigerian (n = 180), Vietnamese (n = 172) and European Caucasian ethnicity (n = 165).
We observed that the genotype distribution of three functional SNP variants (−986 G > A, -602 G > A and -4A > G) differ significantly between the populations investigated (p < 0.0001). The SNP variants were highly linked to each other and revealed significant population patterns. Also the distribution of haplotypes revealed distinct geographical patterns (p < 0.0001).
The observed distribution of the FCN2 functional SNP variants may likely contribute to altered serum ficolin levels and this may depend on the different disease settings in world populations. To conclude, the use of FRET based real-time PCR especially for FCN2 gene will benefit a larger scientific community who extensively depend on rapid, reliable method for FCN2 genotyping.
PMCID: PMC3458960  PMID: 22594803
FRET; Ficolin-2; Genotypes; Haplotypes; Distribution
2.  Mannose Binding Lectin and Susceptibility to Rheumatoid Arthritis in Brazilian Patients and Their Relatives 
PLoS ONE  2014;9(4):e95519.
Rheumatoid arthritis (RA) is a commonly occurring systemic inflammatory auto immune disease and is believed to be associated with genetic factors. The innate immune complement protein Mannose binding lectin (MBL) and their MBL2 genetic variants are associated with different infectious and autoimmune diseases.
In a Brazilian cohort, we aim to associate the functional role of circulating MBL serum levels and MBL2 variants in clinically classified patients (n = 196) with rheumatoid arthritis including their relatives (n = 200) and ethnicity matched healthy controls (n = 200). MBL serum levels were measured by ELISA and functional MBL2 variants were genotyped by direct sequencing.
The exon1+54 MBL2*B variant was significantly associated with an increased risk and the reconstructed haplotype MBL2*LYPB was associated with RA susceptibility. Circulating serum MBL levels were observed significantly lower in RA patients compared to their relatives and controls. No significant contribution of MBL levels were observed with respect to functional class, age at disease onset, disease duration and/or other clinical parameters such as nodules, secondary Sjögren syndrome, anti-CCP and rheumatoid factor. Differential distribution of serum MBL levels with functional MBL2 variants was observed in respective RA patients and their relatives.
Our results suggest MBL levels as a possible marker for RA susceptibility in a Brazilian population.
PMCID: PMC3994105  PMID: 24751721
3.  LRRK2 and RIPK2 Variants in the NOD 2-Mediated Signaling Pathway Are Associated with Susceptibility to Mycobacterium leprae in Indian Populations 
PLoS ONE  2013;8(8):e73103.
In recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. The immunological control of intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1 responses. In this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in Indian population by genotyping four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotypes were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes confer protection in paucibacillary and leprosy patients. The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was observed to contribute towards increased risk whereas haplotypes AA was observed to confer protective role. Our results indicate that a possible shared mechanisms underlying the development of these two clinical forms of the disease as hypothesized. Our findings confirm and validates the role of gene variants involved in NOD2-mediated signalling pathways that play a role in immunological control of intracellular bacteria M. leprae.
PMCID: PMC3756038  PMID: 24015287
4.  IL-4 Haplotype -590T, -34T and Intron-3 VNTR R2 Is Associated with Reduced Malaria Risk among Ancestral Indian Tribal Populations 
PLoS ONE  2012;7(10):e48136.
Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between TH1 and TH2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.
We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).
The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r2>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ23 = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).
Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.
PMCID: PMC3480467  PMID: 23110190

Results 1-4 (4)