背景:结核病(TB)是中国西部地区发病率和死亡率的主要原因之一。临床前研究已经表明来自TB的家族4成员E(CLEC4E)的C型凝集素受体的保护作用。在这里,我们在中国西部汉族人群中调查了CLEC4E基因变异与TB易感性之间的关联.
方法:我们使用改进的多重连接检测反应(iMLDR)方法对CLEC4E基因中的四个单核苷酸多态性(SNP)rs10841856,rs10770847,rs10770855和rs4480590进行了基因分型。900TB病例和1534名健康对照。
结果:在按性别对整个数据进行分层后,发现男性rs10841856的突变等位基因G与Bonferroni校正后的TB风险增加密切相关(OR=1.334,95%CI:1.142-1.560;校正年龄后P<0.001;Bonferroni校正后p=0.001).遗传模型分析发现,rs10841856与显性模型下男性结核病发病风险增加相关(OR=1.557,95%CI=1.228-1.984,校正年龄后P<0.001,Bonferroni校正后P<0.001)。生物信息学分析表明,rs10841856可能落在推定的功能区,可能是CLEC4E和长链非编码RNARP11-561P12.5的表达数量性状基因座(eQTL)。
结论:我们的研究表明,CLEC4E基因中的rs10841856可能与结核病风险增加有关,尤其是中国西部男性汉族个体的显性遗传模型。
BACKGROUND: Tuberculosis (TB) is one of the leading causes of morbidity and mortality in Western China. Preclinical studies have suggested the protective effect of the C-type lectin receptor of family 4 member E (CLEC4E) from TB. Herein, we investigated the association between CLEC4E gene variants and TB susceptibility in a western Chinese Han population.
METHODS: We genotyped four single nucleotide polymorphisms (SNPs) rs10841856, rs10770847, rs10770855 and rs4480590 in the CLEC4E gene using the improved multiplex ligation detection reaction (iMLDR) assay in 900 TB cases and 1534 healthy controls.
RESULTS: After stratifying the whole data by sex, it was found that males exhibited mutant allele G of rs10841856 was more strongly associated with increased TB risk after Bonferroni correction (OR = 1.334, 95% CI: 1.142-1.560; P < 0.001 after adjusting for age; p = 0.001 after Bonferroni correction). The genetic model analysis found that rs10841856 was associated with the increased risk of TB among males under the dominant model (OR = 1.557, 95% CI = 1.228-1.984, P < 0.001 after adjusting for age, P < 0.001 after Bonferroni correction). Bioinformatics analysis suggested that rs10841856 might fall in putative functional regions and might be the expression quantitative trait loci (eQTL) for CLEC4E and long noncoding RNA RP11-561P12.5.
CONCLUSIONS: Our study revealed that rs10841856 in the CLEC4E gene might be related to increased TB risk, especially the dominant genetic model among male Han individuals from Western China.