Heterozygote Advantage of the rs3794624 Polymorphism in CYBA for Resistance to Tuberculosis in Two Chinese Populations

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 subu...

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Veröffentlicht in:Scientific reports 2016-11, Vol.6 (1), p.38213-38213, Article 38213
Hauptverfasser: Liu, Qianqian, Wu, Shouquan, Xue, Miao, Sandford, Andrew J., Wu, Jingcan, Wang, Yu, Chen, Guo, Tao, Chuanmin, Tang, Yin, Feng, Yulin, Luo, Jun, He, Jian-Qing
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container_issue 1
container_start_page 38213
container_title Scientific reports
container_volume 6
creator Liu, Qianqian
Wu, Shouquan
Xue, Miao
Sandford, Andrew J.
Wu, Jingcan
Wang, Yu
Chen, Guo
Tao, Chuanmin
Tang, Yin
Feng, Yulin
Luo, Jun
He, Jian-Qing
description 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.
doi_str_mv 10.1038/srep38213
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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.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep38213</identifier><identifier>PMID: 27901128</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/77 ; 692/308/2056 ; 692/699/255 ; 82/58 ; Adult ; Alleles ; Asian People - genetics ; China ; Female ; Gene Frequency ; Genetic Predisposition to Disease - ethnology ; Genetic Predisposition to Disease - genetics ; Genotype ; Heterogeneity ; Heterozygote ; Heterozygote advantage ; Humanities and Social Sciences ; Humans ; Male ; Microorganisms ; Middle Aged ; multidisciplinary ; NAD(P)H oxidase ; NADPH Oxidases - genetics ; NADPH-diaphorase ; Oxidation ; Polymorphism, Single Nucleotide ; Reactive oxygen species ; Science ; Single-nucleotide polymorphism ; Tuberculosis ; Tuberculosis - ethnology ; Tuberculosis - genetics ; Young Adult</subject><ispartof>Scientific reports, 2016-11, Vol.6 (1), p.38213-38213, Article 38213</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Nov 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-813d7e9a2a022e1e9c4d9a3bf15efc303a936a79110f90bc62e6bfde983fed633</citedby><cites>FETCH-LOGICAL-c504t-813d7e9a2a022e1e9c4d9a3bf15efc303a936a79110f90bc62e6bfde983fed633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128811/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128811/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27928,27929,41124,42193,51580,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27901128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Qianqian</creatorcontrib><creatorcontrib>Wu, Shouquan</creatorcontrib><creatorcontrib>Xue, Miao</creatorcontrib><creatorcontrib>Sandford, Andrew J.</creatorcontrib><creatorcontrib>Wu, Jingcan</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Chen, Guo</creatorcontrib><creatorcontrib>Tao, Chuanmin</creatorcontrib><creatorcontrib>Tang, Yin</creatorcontrib><creatorcontrib>Feng, Yulin</creatorcontrib><creatorcontrib>Luo, Jun</creatorcontrib><creatorcontrib>He, Jian-Qing</creatorcontrib><title>Heterozygote Advantage of the rs3794624 Polymorphism in CYBA for Resistance to Tuberculosis in Two Chinese Populations</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>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. 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Wu, Shouquan ; Xue, Miao ; Sandford, Andrew J. ; Wu, Jingcan ; Wang, Yu ; Chen, Guo ; Tao, Chuanmin ; Tang, Yin ; Feng, Yulin ; Luo, Jun ; He, Jian-Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-813d7e9a2a022e1e9c4d9a3bf15efc303a936a79110f90bc62e6bfde983fed633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>45/77</topic><topic>692/308/2056</topic><topic>692/699/255</topic><topic>82/58</topic><topic>Adult</topic><topic>Alleles</topic><topic>Asian People - genetics</topic><topic>China</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Predisposition to Disease - ethnology</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Heterogeneity</topic><topic>Heterozygote</topic><topic>Heterozygote advantage</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Male</topic><topic>Microorganisms</topic><topic>Middle Aged</topic><topic>multidisciplinary</topic><topic>NAD(P)H oxidase</topic><topic>NADPH Oxidases - genetics</topic><topic>NADPH-diaphorase</topic><topic>Oxidation</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Reactive oxygen species</topic><topic>Science</topic><topic>Single-nucleotide polymorphism</topic><topic>Tuberculosis</topic><topic>Tuberculosis - ethnology</topic><topic>Tuberculosis - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Qianqian</creatorcontrib><creatorcontrib>Wu, Shouquan</creatorcontrib><creatorcontrib>Xue, Miao</creatorcontrib><creatorcontrib>Sandford, Andrew J.</creatorcontrib><creatorcontrib>Wu, Jingcan</creatorcontrib><creatorcontrib>Wang, Yu</creatorcontrib><creatorcontrib>Chen, Guo</creatorcontrib><creatorcontrib>Tao, Chuanmin</creatorcontrib><creatorcontrib>Tang, Yin</creatorcontrib><creatorcontrib>Feng, Yulin</creatorcontrib><creatorcontrib>Luo, Jun</creatorcontrib><creatorcontrib>He, Jian-Qing</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27901128</pmid><doi>10.1038/srep38213</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record>
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subjects 45/77
692/308/2056
692/699/255
82/58
Adult
Alleles
Asian People - genetics
China
Female
Gene Frequency
Genetic Predisposition to Disease - ethnology
Genetic Predisposition to Disease - genetics
Genotype
Heterogeneity
Heterozygote
Heterozygote advantage
Humanities and Social Sciences
Humans
Male
Microorganisms
Middle Aged
multidisciplinary
NAD(P)H oxidase
NADPH Oxidases - genetics
NADPH-diaphorase
Oxidation
Polymorphism, Single Nucleotide
Reactive oxygen species
Science
Single-nucleotide polymorphism
Tuberculosis
Tuberculosis - ethnology
Tuberculosis - genetics
Young Adult
title Heterozygote Advantage of the rs3794624 Polymorphism in CYBA for Resistance to Tuberculosis in Two Chinese Populations
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