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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >LARGE-SCALE CANDIDATE GENE STUDY OF TUBERCULOSIS SUSCEPTIBILITY IN THE KARONGA DISTRICT OF NORTHERN MALAWI.
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LARGE-SCALE CANDIDATE GENE STUDY OF TUBERCULOSIS SUSCEPTIBILITY IN THE KARONGA DISTRICT OF NORTHERN MALAWI.

机译：马拉维北部卡隆加地区结核菌易感性的大型候选基因研究。

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Twenty-seven polymorphisms from 12 genes have been investigated for association with tuberculosis (TB) in up to 514 cases and 913 controls from Karonga district, northern Malawi. Homozygosity for the complement receptor 1 (CR1) Q1022H polymorphism was associated with susceptibility to TB in this population (odds ratio [OR] = 3.12, 95% Confidence interval [CI] = 1.13-8.60, P = 0.028). This association was not observed among human immunodeficiency virus (HIV)-positive TB cases, suggesting either chance association or that HIV status may influence genetic associations with TB susceptibility. Heterozygosity for a newly studied CAAA insertion/deletion polymorphism in the 3'-untranslated region of solute carrier family 11, member 1 (SLC11A1, formerly NRAMP1) was associated with protection against TB in both HIV-positive (OR = 0.70, 95% CI = 0.49-0.99, P = 0.046) and HIV-negative (OR = 0.65, 95% CI = 0.46-0.92, P = 0.014) TB cases, suggesting that the SLC11A1 protein may have a role in innate TB immune responses that influence susceptibility even in immunocompromised individuals. However, associations of other variants of SCLA11A with TB reported from other populations were not replicated in Malawi. Furthermore, associations with vitamin D receptor, interferon-gamma, and mannose-binding lectin observed elsewhere were not observed in this Karonga study. Genetic susceptibility to TB in Africans appears polygenic. The relevant genes and variants may vary significantly between populations, and may be affected by HIV infection status.
机译：来自马拉维北部卡隆加区的多达514例病例和913例对照研究了12种基因的27个多态性与结核病（TB）的关联。补体受体1（CR1）Q1022H多态性的纯合性与该人群对结核病的易感性相关（比值比[OR] = 3.12，95％置信区间[CI] = 1.13-8.60，P = 0.028）。在人类免疫缺陷病毒（HIV）阳性结核病例中未观察到这种关联，表明机会关联或HIV状况可能影响与结核易感性的遗传关联。新研究的溶质载体家族11成员3'-非翻译区CAAA插入/缺失多态性的杂合性与HIV阳性（OR = 0.70，95％CI）中的TB保护相关= 0.49-0.99，P = 0.046）和HIV阴性（OR = 0.65，95％CI = 0.46-0.92，P = 0.014）结核病例，这表明SLC11A1蛋白可能在先天性TB免疫反应中影响易感性即使是免疫力低下的人但是，马拉维未复制其他人群报告的SCLA11A其他变异与结核的关联。此外，在这项Karonga研究中未观察到与维生素D受体，干扰素-γ和甘露糖结合的凝集素的相关性。非洲人对结核病的遗传易感性似乎是多基因的。相关基因和变异体在人群之间可能有很大差异，并且可能会受到HIV感染状况的影响。

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