RESUMEN

Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH+) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH+; 190 DTH-; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH+/- status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH+ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P=0.005; 95% CI=1.28-3.97) and TGFBI (OR 1.94; P=0.003; 95% CI=1.24-3.03). VL child/parent trios gave no evidence of association, but the DTH- phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P=0.006; 95% CI=1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P=0.042; 95% CI=1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil.

Asunto(s)

Cromosomas Humanos Par 5/genética , Hipersensibilidad Tardía/genética , Leishmania infantum , Leishmaniasis Visceral/genética , Leishmaniasis Visceral/inmunología , Polimorfismo de Nucleótido Simple , Alelos , Animales , Brasil , Estudios de Casos y Controles , Biología Computacional , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leishmaniasis Visceral/parasitología , Modelos Logísticos , Masculino , Fenotipo , Alineación de Secuencia

RESUMEN

A genome-wide scan was conducted for visceral leishmaniasis (VL) in Brazil. Initially, 405 markers were typed in 22 multicase pedigrees (28 nuclear families; 174 individuals; 66 affected). Non-parametric multipoint analysis detected nine chromosomal regions with provisional evidence (logarithm of the odds (LOD) scores 0.95-1.66; 0.003

Asunto(s)

Predisposición Genética a la Enfermedad , Genoma Humano , Leishmaniasis Visceral/genética , Leishmaniasis Visceral/inmunología , Brasil , Quimiocina CCL1 , Quimiocinas CC/genética , Humanos , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple