02504nas a2200421   4500000000100000008004100001260001300042653002400055653002500079653002000104653001100124653003100135653002000166653003800186653001100224653001900235653001200254653002800266653000900294653002700303653002500330653003600355653003000391100001600421700002300437700001600460700002400476700001800500700001600518700002300534700001600557700001500573245017800588300001100766490000700777520128400784022001402068       2009                            d  c2009 Mar10aAntigens, Bacterial10aCase-Control Studies10aChronic Disease10aFemale10aGene Expression Regulation10aGenetic Markers10aGenetic Predisposition to Disease10aHumans10aInterleukin-1010aleprosy10aLeukocytes, Mononuclear10aMale10aMolecular Epidemiology10aMycobacterium leprae10aPolymorphism, Single Nucleotide10aPromoter Regions, Genetic1 aPEREIRA A C1 aBrito-de-Souza V N1 aCardoso C C1 aDias-Baptista I M F1 aParelli F P C1 aVenturini J1 aVillani-Moreno F R1 aPacheco A G1 aMoraes M O00aGenetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for -819C/T in leprosy susceptibility.  a174-800 v103 a<p>Leprosy is a complex infectious disease influenced by genetic and environmental factors. The genetic contributing factors are considered heterogeneous and several genes have been consistently associated with susceptibility like PARK2, tumor necrosis factor (TNF), lymphotoxin-alpha (LTA) and vitamin-D receptor (VDR). Here, we combined a case-control study (374 patients and 380 controls), with meta-analysis (5 studies; 2702 individuals) and biological study to test the epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic markers in leprosy. We observed that the -819T allele is associated with leprosy susceptibility either in the case-control or in the meta-analysis studies. Haplotypes combining promoter single-nucleotide polymorphisms also implicated a haplotype carrying the -819T allele in leprosy susceptibility (odds ratio (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood mononuclear cells stimulated with Mycobacterium leprae antigens and found that -819T carriers produced lower levels of IL-10 when compared with non-carriers. Taken together, these data suggest that low levels of IL-10 during the disease outcome can drive patients to a chronic and unprotective response that culminates with leprosy.</p>  a1476-5470