Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection

S. M.B. Jeronimo, A. K.B. Holst, S. E. Jamieson, R. Francis, D. R.A. Martins, F. L. Bezerra, N. A. Ettinger, E. T. Nascimento, G. R. Monteiro, H. G. Lacerda, E. N. Miller, H. J. Cordell, P. Duggal, T. H. Beaty, J. M. Blackwell, M. E. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)539-551
Number of pages13
JournalGenes and immunity
Volume8
Issue number7
DOIs
StatePublished - Oct 2007

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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