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

Genes at human chromosome 5q31.1 regulate delayed-type hypersensitivity responses associated with Leishmania chagasi infection.
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DOI:
10.1038/sj.gene.6364422
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发表时间:
2007-10
期刊:
影响因子:
5
通讯作者:
Wilson, M. E.
Wilson, M. E.
中科院分区:
医学3区
文献类型:
--
作者:
Jeronimo, S. M. B.;Holst, A. K. B.;Jamieson, S. E.;Francis, R.;Martins, D. R. A.;Bezerra, F. L.;Ettinger, N. A.;Nascimento, E. T.;Monteiro, G. R.;Lacerda, H. G.;Miller, E. N.;Cordell, H. J.;Duggal, P.;Beaty, T. H.;Blackwell, J. M.;Wilson, M. E.

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由恰加斯利什曼原虫引起的内脏利什曼病 (VL) 是巴西东北部的地方病。迟发性超敏反应皮试反应 (DTH+) 呈阳性是获得性抗病能力的标志,具有家族聚集性,并且可能受到基因控制。对巴西东北部 VL 流行地区 102 个家系(323 个 DTH+;190 个 DTH−;123 个 VL 个体)的细胞因子 5q23.3-q31.1 区域 IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI 中的 23 个单核苷酸多态性 (SNP) 进行了基因分型。使用基于家族的逐步条件逻辑回归分析来分析 20 个 SNP 的数据与 DTH+/- 状态和 VL 的关联。在 LECT2(OR 2.25;P=0.005;95% CI=1.28-3.97)和 TGFBI(OR 1.94;P=0.003;95% CI=1.24-3.03)中,观察到 DTH+ 表型与单独连锁不平衡块中的标记之间存在独立关联。 VL儿童/父母三人组没有提供连锁和关联的证据,但DTH-表型与IL4处的SNP rs2070874相关(OR 3.14;P=0.006;95% CI=1.38-7.14),以及LECT2和TGFBI之间的SNP rs30740相关(OR 3.00;P=0.042;95%) CI=1.04-8.65)。这些结果表明 5q23.3-q31.1 免疫反应基因簇中的几个基因影响巴西该地区恰加西乳杆菌感染的结果。
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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作者:
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