Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis

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. 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 216 TB patients and 275 healthy subjects by ligase detection reaction technique. 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. In 1.7 kb IRGM promoter region, only − 1208A/G polymorphism is associated with susceptibility to TB.