肺结核患者发生乙型肝炎病毒共感染遗传易感性的全基因组关联分析

Genome-wide association analysis of genetic susceptibility to hepatitis B virus co-infection in patients with pulmonary tuberculosis

目的在中国汉族肺结核患者中进行全基因组关联分析(genome-wide association study,GWAS),以探究与肺结核患者发生乙型肝炎(乙肝)病毒共感染密切相关的单基因位点突变。方法利用Illumina Human Omni Express基因芯片分型实验平台对2013年3月—2018年3月间纳入的946例肺结核患者进行全基因组基因分型。经质量控制后共703例单一结核感染患者和53例结核乙肝合并感染患者的389 972个单核苷酸多态性(single nucleotide polymorphism,SNP)纳入后续关联分析。结果统计学关联信号最强的SNP是位于8p23.1染色体上的rs118122819(P=2.923×10-12,比值比=7.933),其他潜在的易感基因还包括CDH4(rs73309833)、MARCH1(rs3797020)和DNER(rs13393112)等。rs118122819与rs4840365之间存在强连锁不平衡关系(D’=0.88,r2=0.76),而rs4840365则位于MFHAS1基因区域。结论该研究为结核患者发生乙肝共感染的易感基因位点的存在提供了证据,可为结核乙肝共感染的机制研究、疾病预防和治疗对策提供重要线索。但必须在更大规模的研究中复制和验证这些关联。

Objective To explore the single locus mutation that related to hepatitis B virus(HBV)co-infection by means of genome-wide association study(GWAS)in Chinese Han patients with pulmonary tuberculosis(TB).Methods A total of 946 patients with pulmonary TB enrolled between March 2013 and March 2018 were genotyped by Illumina Human Omni Express gene chip.After quality control,389 972 single nucleotide polymorphisms(SNPs)of 703 patients with single TB infection and 53 patients with TB-HBV co-infection were included in the follow-up association analysis.Results The SNP with the strongest statistical correlation signal was rs118122819(P=2.923×10-12,odds ratio=7.933)located on chromosome 8 p23.1.Other potential susceptibility genes included CDH4(rs73309833),MARCH1(rs3797020),and DNER(rs13393112),etc.In addition,a strong linkage imbalance between rs118122819 and rs4840365(D’=0.88,r2=0.76)was found,while rs4840365 was located in the MFHAS1 gene region.Conclusions This study provides evidence for the presence of susceptibility gene locus for HBV co-infection in pulmonary TB patients,and provides important clues for the mechanism research,disease prevention,and treatment of co-infection.But these associations must be replicated and validated in larger studies.