Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection.
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.
Jeronimo
S M B
SM
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, Brazil.
Holst
A K B
AK
Jamieson
S E
SE
Francis
R
R
Martins
D R A
DR
Bezerra
F L
FL
Ettinger
N A
NA
Nascimento
E T
ET
Monteiro
G R
GR
Lacerda
H G
HG
Miller
E N
EN
Cordell
H J
HJ
Duggal
P
P
Beaty
T H
TH
Blackwell
J M
JM
Wilson
M E
ME
D000483:Alleles; D000818:Animals; D001938:Brazil; D016022:Case-Control Studies; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000235:genetics*; D018314:Leishmania infantum; D007898:Leishmaniasis, Visceral / Q000235:genetics* / Q000276:immunology* / Q000469:parasitology; D016015:Logistic Models; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment
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