title: Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis.
abstract: BACKGROUND
  Human immunity-related GTPase M (IRGM) is found to play an important role in defense against intracellular pathogen Mycobacterium tuberculosis in vitro by regulating autophagy. To verify whether single nucleotide polymorphisms (SNPs) in the promoter region of IRGM gene are associated with tuberculosis (TB) 1.7 kb IRGM promoter region was sequenced and SNP analysis was conducted in TB patients and healthy controls.
  
  
  METHODS
  A simple and rapid procedure for extracting DNA from clotted-blood was developed in this study. A 1.7 kb IRGM promoter region was amplified and sequenced for nucleotide polymorphism search. Then, 3 SNPs were selected and analyzed in 216TB patients and 275 healthy subjects by ligase detection reaction technique.
  
  
  RESULTS
  DNA extracted by our method was of high quality and suitable for PCR, sequencing, and genotyping. We identified 29 polymorphisms in the 1.7 kb IRGM promoter region, including 11 novel polymorphisms not yet reported. Large population analysis showed that frequencies of -1208A allele (P=0.031), -1208AA genotype (P=0.042), and -1208A/-1161C/-947C (P=0.035) and -1208G/-1161C/-947C (P=0.030) haplotypes in cases were significantly different from those in controls.
  
  
  CONCLUSIONS
  In 1.7 kb IRGM promoter region, only -1208A/G polymorphism is associated with susceptibility to TB.
authors.affiliation: Department of Bacteriology and Immunology, Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou District, Beijing 101149, PR China.
authors.forename: Nanying
authors.initials: N
authors.lastname: Che
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Tiejie
authors.initials: T
authors.lastname: Gao
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuefei
authors.initials: Y
authors.lastname: Han
authors.forename: Xuxia
authors.initials: X
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Sun
authors.forename: Jianyuan
authors.initials: J
authors.lastname: Zhang
authors.forename: Weicong
authors.initials: W
authors.lastname: Ren
authors.forename: Miao
authors.initials: M
authors.lastname: Tian
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Wensheng
authors.initials: W
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.forename: Chuanyou
authors.initials: C
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D019204:GTP-Binding Proteins; C513539:IRGM protein, human