title: IRGM gene polymorphisms and haplotypes associate with susceptibility of pulmonary tuberculosis in Chinese Hubei Han population.
abstract: Human immunity-related GTPase M (IRGM) is found to play an important role in defense against intracellular pathogen Mycobacterium tuberculosis (M. tuberculosis) in vitro by regulating autophagy. The objective of the study was to determine the association between IRGM polymorphisms and susceptibility to pulmonary tuberculosis (PTB) in Chinese Hubei Han population. In this study, 237 PTB patients and 269 healthy controls were screened for IRGM promoter single nucleotide polymorphisms (SNPs) by gene sequencing, and an association study was performed. A luciferase assay was used to determine the transcriptional activity of the promoter polymorphism. The relative expression level of IRGM gene was measured by Real time Quantitative PCR (qRT-PCR). We identified 3 polymorphisms [-1208 (rs4958842), -1161 (rs4958843), and -947 (rs4958846)] in the IRGM promoter region. Our finding showed that the IRGM -947 CT genotype as well as CC genotype decreased the risk of PTB in comparison with TT genotype (OR = 0.216, 95% CI = 0.141-0.331,P < 0.001 and OR = 0.167, 95% CI = 0.088-0.318, P < 0.001,respectively). The -947C allele decreased the risk of PTB in comparison with T allele (OR = 0.266, 95% CI = 0.196-0.362, P < 0.001). There was linkage disequilibrium between these three IRGM SNPs and we further analyzed the haplotypes of these SNPs. Six haplotypes were identified and we found that the haplotype ACC played a protective role in the susceptibility to PTB. In contrast, the ACT haplotype was associated with an increased susceptibility to PTB. In addition, the ACT haplotype reduced the relative luciferase activity of IRGM promoter and decreased the expression of IRGM in PTB patients. Our findings indicated that IRGM functional polymorphisms and haplotypes in promoter were associated with the susceptibility to PTB in Chinese Hubei Han population.
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Leyong
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China.
authors.forename: Zunqiong
authors.initials: Z
authors.lastname: Ke
authors.affiliation: Department of Clinical Laboratory, Wuhan Medical Treatment Center, Wuhan, Hubei Province, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Epidemiology, Wuhan University School of Public Health, Wuhan, Hubei Province, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, PR China. Electronic address: yanlitif1120@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002460:Cell Line; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014162:Transfection; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology
chemical_list: D005819:Genetic Markers; D019204:GTP-Binding Proteins; C513539:IRGM protein, human
keywords: Immunity-related GTPase M; Polymorphisms; Pulmonary tuberculosis; Susceptibility