TY - JOUR KW - Antigens, Bacterial KW - Case-Control Studies KW - Chronic Disease KW - Female KW - Gene Expression Regulation KW - Genetic Markers KW - Genetic Predisposition to Disease KW - Humans KW - Interleukin-10 KW - leprosy KW - Leukocytes, Mononuclear KW - Male KW - Molecular Epidemiology KW - Mycobacterium leprae KW - Polymorphism, Single Nucleotide KW - Promoter Regions, Genetic AU - PEREIRA A C AU - Brito-de-Souza V N AU - Cardoso C C AU - Dias-Baptista I M F AU - Parelli F P C AU - Venturini J AU - Villani-Moreno F R AU - Pacheco A G AU - Moraes M O AB -

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.

BT - Genes and immunity C1 - http://www.ncbi.nlm.nih.gov/pubmed/19110537?dopt=Abstract DA - 2009 Mar DO - 10.1038/gene.2008.97 IS - 2 J2 - Genes Immun. LA - eng N2 -

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.

PY - 2009 SP - 174 EP - 80 T2 - Genes and immunity TI - Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for -819C/T in leprosy susceptibility. VL - 10 SN - 1476-5470 ER -