title: Heterozygote Advantage of the rs3794624 Polymorphism in CYBA for Resistance to Tuberculosis in Two Chinese Populations.
abstract: Phagocyte Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase complex is a key enzyme that catalyzes the production of reactive oxygen species, which mediate oxygen-dependent killing of microorganisms, such as Mycobacterium tuberculosis. P22phox, encoded by CYBA, is the key regulatory subunit of NADPH oxidase. Our study aimed to investigate the association of CYBA polymorphisms with susceptibility to tuberculosis. Three SNPs (rs9932581, rs3794624 and rs4673) were genotyped in the discovery cohort composed of Chinese Han individuals. We found that the A allele of rs3794624 was a significant protective factor against tuberculosis (GA vs. GG: OR = 0.74, 95% CI 0.57-0.96; GA vs. GG+AA: OR = 0.73, 95% CI 0.56-0.95), which was then replicated in the Chinese Tibetan population (GA vs. GG: OR = 0.68, 95% CI 0.51-0.92; AA+GA vs. GG: OR = 0.70, 95% CI 0.52-0.93; GA vs. GG+AA: OR = 0.68, 95% CI 0.51-0.92). Meta-analysis including both cohorts identified overdominance as the best genetic model and provided robust evidence for the protective effect of the rs3794624 GA genotype against tuberculosis without any evidence of heterogeneity (GA vs. GG+AA: OR = 0.71, 95% CI 0.58-0.86). Our study found an association between the GA genotype of rs3794624 in CYBA with decreased tuberculosis susceptibility in two Chinese populations. Further analyses are needed to reveal the potential function of this SNP.
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.|Department of Respiratory Diseases, Chengdu Municipal First People's Hospital, Chengdu, Sichuan, China.|Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Shouquan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Xue
authors.affiliation: Centre for Heart Lung Innovation, University of British Columbia and St. Paul's Hospital, Vancouver, BC, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Sandford
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jingcan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Geriatrics, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Chuanmin
authors.initials: C
authors.lastname: Tao
authors.affiliation: State Key Laboratory of Oral Disease, West China School &Hospital of Stomotology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Infectious Diseases, People's Hospital of Aba Tibetan Autonomous Prefecture, Maer, Sichuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: He
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000208:ethnology / Q000235:genetics*; D055815:Young Adult
chemical_list: D019255:NADPH Oxidases; C086986:CYBA protein, human