Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection

S M B Jerônimo; 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

doi:10.1038/sj.gene.6364422

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Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection

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Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection

S M B Jerônimo, 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, …

Genes and immunity, Vol.8(7), pp.539-551

10/2007

DOI: 10.1038/sj.gene.6364422

PMCID: PMC2435172

PMID: 17713557

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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 analysed 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 linkage and 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.

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Title: Subtitle: Genes at Human Chromosome 5q31.1 Regulate Delayed Type Hypersensitivity Responses Associated with Leishmania chagasi Infection
Creators: S M B Jerônimo - Universidade Federal do Rio Grande do Norte
A K B Holst - University of Iowa
S E Jamieson - University of Cambridge
R Francis - University of Cambridge
D R A Martins - Universidade Federal do Rio Grande do Norte
F L Bezerra
N A Ettinger - Universidade Federal do Rio Grande do Norte
E T Nascimento - Universidade Federal do Rio Grande do Norte
G R Monteiro - Universidade Federal do Rio Grande do Norte
H G Lacerda - Universidade Federal do Rio Grande do Norte
E N Miller - University of Cambridge
H J Cordell - Newcastle University
P Duggal - National Human Genome Research Institute
T H Beaty - Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD
J M Blackwell - University of Cambridge
M E Wilson - University of Iowa
Resource Type: Journal article
Publication Details: Genes and immunity, Vol.8(7), pp.539-551
DOI: 10.1038/sj.gene.6364422
PMID: 17713557
PMCID: PMC2435172
NLM abbreviation: Genes Immun
ISSN: 1466-4879
eISSN: 1476-5470
Grant note: 074196 || WT / Wellcome Trust :
Language: English
Date published: 10/2007
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001149002771

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