Estudo de Associação entre o Gene VDR e a Hanseníase

摘要: Leprosy is a chronic infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. The success of infection occurs due to ability bacteria to subvert immune system, slowly proliferating in skin macrophages and Schwann cells in peripheral nerves. It known that majority exposed people do not develop leprosy bacillus, epidemiological evidence has shown conclusively genes influence the outcome disease. Accordingly, several studies have searched for variations genes involved response M. leprae, which could explain susceptibility/resistance of certain individuals This present study aimed analyze possible association between genetic markers VDR gene (Vitamin D Receptor) leprosy per se. VDR gene been related diseases, its important role antimicrobial pathways mediated vitamin D. To this end, we used population-based case-control study with 416 patients 587 controls as well replication using families 365 individuals, comprising 90 nuclear families. Fok, rs4760658 Taq polymorphisms were evaluated, resulting allele, genotype haplotype frequencies were compared between cases controls. In family study, transmission disequilibrium test (TDT) evaluate alleles haplotypes above mentioned SNPs to offspring affected association with leprosy. Through systematic review were gathered informative between polymorphism leprosy, aiming meta-analysis study. Our results show CT Fok SNP was associated protection value OR (Odds Ratio) equal 0.77, but the significance level considered “borderline” when adjusted covariates gender and ethnicity (p = 0.05). For Taq, controls were statistically different, values 0.96 (p=0,85) 0.79 (p=0,35) respectively. TDT indicated no significant Taq and leprosy, latter exhibiting p-value 0,09. However, case-control study analysis combination Fok/rs4760658/Taq haplotype C/C/C protective (OR 0.46, p 0.02), whereas T/T/T haplotype was associated 0.62, 0.04). of haplotype Fok/Taq while it "borderline" T/T, followed same direction case-control, suggesting protection. Although four found after review, all needed be excluded, either deviate from Hardy-Weinberg equilibrium or different experimental design, precluding meta-analysis. Thus, work lets us conclude an C/C/C of borderline the haplotype T/T/T disease, requires confirmation either new studies or increasing number along locus.