title: Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis.
abstract: Genetic factors affect host susceptibility to pathogens. In this population-based case control study, we explored the genetic polymorphisms of IL-17, TLR4 and miR-146a in association with pulmonary tuberculosis in a Chinese Han population. We recruited 1601 pulmonary tuberculosis patients matched with 1526 healthy controls and genotyped twelve functional single nucleotide polymorphisms (SNPs). After the correction for multiple comparisons, two SNPs (rs10759932 and rs2737190) in the TLR4 gene remained significant. Individuals carrying the rs2737190-AG genotype (vs. AA) had a significantly increased risk of either clinical tuberculosis (OR: 1.31, 95% CI: 1.11-1.53) or sputum smear-positive tuberculosis (OR: 1.35, 95% CI: 1.13-1.61). Stratification analysis revealed that the effects of genetic variations on tuberculosis were more evident among non-smokers. People with haplotype TLR4 rs10983755G-rs10759932C had a significantly increased risk of tuberculosis (OR: 3.43, 95% CI: 2.34-5.05). Moreover, we found that SNPs of rs3819024 in IL-17A and rs763780 in IL-17F were weakly related to a prognosis of tuberculosis. Our results suggest that genetic polymorphisms of IL-17 and TLR4 may play a role in host susceptibility to tuberculosis in the Chinese Han population. More work is necessary to identify specific causative variants of tuberculosis underlying the observed associations.
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Lingshuang
authors.initials: L
authors.lastname: Lü
authors.affiliation: Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang, 212005 PR China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Tuberculosis, Third Hospital of Zhenjiang City, Zhenjiang, 212005 PR China.
authors.forename: Hongqiu
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, 171 77 Stockholm, Sweden.|Health Care Services, Stockholm County Council, 171 77 Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Burstrom
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, 171 77 Stockholm, Sweden.|Health Care Services, Stockholm County Council, 171 77 Stockholm, Sweden.|Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Burstrom
authors.affiliation: Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|Department of Social Medicine and Health Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.|The Innovation Center for Social Risk Governance in Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Wang
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012306:Risk; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics
chemical_list: C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4