title: Association of autophagy-related IRGM polymorphisms with latent versus active tuberculosis infection in a Chinese population.
abstract: The autophagy-related immunity-related GTPase family M protein, IRGM, plays an important role in the defense against tuberculosis (TB) infection. IRGM polymorphisms are associated with TB infection susceptibility, and recent studies demonstrate host genetic differences between active and latent TB. Here, we investigated the association between IRGM polymorphisms and TB infection type in a Chinese population. We recruited 268 and 321 patients with confirmed or latent TB, respectively, and 475 TB-free healthy controls. Three single nucleotide polymorphisms, rs10065172, rs10051924, and rs13361189 within IRGM were genotyped using TaqMan-based assays. Interferon-gamma release levels were tested by T-SPOT. rs10065172 (P = 0.024, OR 0.67 (95% CI 0.48-0.95)), rs10051924 (P = 0.01, OR 0.64 (95% CI 0.46-0.90)), and rs13361189 (P = 0.055, OR 0.72 (95% CI 0.51-1.01)) were associated with a protective role against latent TB progression. Haplotype analysis showed that TCC was protective for latent TB (P = 0.022, OR 0.74 (95% CI 0.57-0.96)) whereas TTC conferred a higher risk of active TB. Additionally, patients with the rs10065172 TT genotype had a higher response to TB specific antigens. Thus, IRGM polymorphism differences between latent and active TB suggests that genetic differences in autophagy might partly affect host TB infection status.
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: tjhwangxiong@163.com.
authors.forename: Xiong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D001343:Autophagy / Q000235:genetics*; D001431:Bacteriological Techniques; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D018450:Disease Progression; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D054884:Host-Pathogen Interactions; D006801:Humans; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D019204:GTP-Binding Proteins; C513539:IRGM protein, human
keywords: Autophagy; IRGM; Infection; Polymorphism; Tuberculosis