title: Relationship of the p22phox (CYBA) gene polymorphism C242T with risk of coronary artery disease: a meta-analysis.
abstract: BACKGROUND
  Observational and experimental studies have thus far been unable to resolve whether the CYBA C242T polymorphism is associated with coronary artery disease (CAD). Therefore, we undertook a comprehensive meta-analysis to more precisely evaluate the influence of this polymorphism on CAD and potential biases.
  
  
  METHODS
  We screened MEDLINE, Embase, CNKI, Wanfang and CBM up to January 2013 and extracted data from 22 studies with 9,279 CAD patients and 9,349 controls. A random-effects model was exploited to synthesize the inconsistent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias.
  
  
  RESULTS
  The CYBA C242T polymorphism conformed to Hard-Weinberg Equilibrium for all studies (P>0.05). Overall comparison of the T allele with the C allele produced a non-significant risk estimate for CAD but with striking heterogeneity (T versus C: P = 0.87, OR = 0.99, 95%CI 0.89-1.11, P(heterogeneity)<0.0001, I² = 67.8%). However, subgroup analysis by ethnicity documented that the T allele carriers had a marginal risk increase (21%) of CAD among Caucasians (recessive genetic model: P = 0.05, 95%CI 1.00-1.46, P(heterogeneity) = 0.15, I² = 29.1%). Then data were divided into study design, the significance of CAD risk increase was substantially strengthened in matched case-control studies (allele comparison: P = 0.02, OR = 1.13, 95%CI 1.02-1.26, P(heterogeneity) = 0.24, I² = 21.6%).Further meta-regression analysis identified that a large proportion of heterogeneity was explained by body mass index (BMI) (P = 0.03, OR = 1.07, 95%CI 1.01-1.15) and study design (P = 0.03, OR = 1.30, 95%CI 1.02-1.64).There was no obvious publication bias as verified by funnel plot and Egger's linear regression test (t = -0.25, P = 0.81 for allele comparison).
  
  
  CONCLUSIONS
  Taken together, our results suggested the CYBA C242T polymorphism might be a risk-conferring factor on developing CAD and BMI and study design were probable sources of between-study heterogeneity.
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wu
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Lou
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Chen
authors.forename: Yucai
authors.initials: Y
authors.lastname: Xie
authors.forename: Guoping
authors.initials: G
authors.lastname: Lu
mesh_terms: D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019255:NADPH Oxidases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D019255:NADPH Oxidases; C086986:CYBA protein, human
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: Atherosclerosis. 2004 Jan;172(1):167-73
references.pmid: 14709372
references.citation: JAMA. 2007 Apr 11;297(14):1551-61
references.pmid: 17426274
references.citation: Am J Hum Genet. 2004 Dec;75(6):966-78
references.pmid: 15467980
references.citation: Thromb Res. 2012 Nov;130(5):e259-65
references.pmid: 23040216
references.citation: J Clin Invest. 1990 Nov;86(5):1729-37
references.pmid: 2243141
references.citation: Psychol Methods. 2003 Sep;8(3):243-53
references.pmid: 14596489
references.citation: PLoS Med. 2012;9(5):e1001212
references.pmid: 22563304
references.citation: Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R117-23
references.pmid: 16987874
references.citation: Ann Intern Med. 1997 Nov 1;127(9):820-6
references.pmid: 9382404
references.citation: Trends Genet. 2004 Sep;20(9):439-44
references.pmid: 15313553
references.citation: J Clin Epidemiol. 2009 Feb;62(2):188-94
references.pmid: 18722087
references.citation: Clin Physiol. 2001 Nov;21(6):718-22
references.pmid: 11722480
references.citation: Atherosclerosis. 2010 Oct;212(2):534-8
references.pmid: 20598694
references.citation: PLoS Med. 2009 Jul 21;6(7):e1000097
references.pmid: 19621072
references.citation: Nature. 2009 Sep 24;461(7263):489-94
references.pmid: 19779445
references.citation: Atherosclerosis. 2011 Nov;219(1):218-23
references.pmid: 21855067
references.citation: Int J Cardiol. 2004 Jun;95(2-3):145-51
references.pmid: 15193812
references.citation: Free Radic Res. 2008 Jan;42(1):82-92
references.pmid: 18324526
references.citation: J Clin Epidemiol. 2003 Apr;56(4):297-303
references.pmid: 12767405
references.citation: J Am Coll Cardiol. 2011 May 10;57(19):e215-367
references.pmid: 21545940
references.citation: Eur J Clin Invest. 1999 Dec;29(12):999-1002
references.pmid: 10583446
references.citation: Am J Med Genet. 1999 Sep 3;86(1):57-61
references.pmid: 10440830
references.citation: J Biol Chem. 1996 Sep 20;271(38):23317-21
references.pmid: 8798532
references.citation: Wei Sheng Yan Jiu. 2004 Jul;33(4):443-6
references.pmid: 15461271
references.citation: Am Heart J. 2007 Apr;153(4):640.e1-6
references.pmid: 17383305
references.citation: Circulation. 2003 Oct 28;108(17):2034-40
references.pmid: 14581381
references.citation: Circulation. 2003 Oct 21;108(16):1912-6
references.pmid: 14568884
references.citation: Am J Hum Genet. 2004 May;74(5):827-45
references.pmid: 15077202
references.citation: Coron Artery Dis. 2007 Aug;18(5):339-46
references.pmid: 17627182
references.citation: Am J Epidemiol. 1999 Apr 15;149(8):706-11
references.pmid: 10206619
references.citation: Circulation. 1998 Jan 20;97(2):135-7
references.pmid: 9445163
references.citation: BMJ. 1997 Sep 13;315(7109):629-34
references.pmid: 9310563
references.citation: Circulation. 2011 May 10;123(18):e426-579
references.pmid: 21444888
references.citation: Heart Vessels. 2010 May;25(3):229-36
references.pmid: 20512451
references.citation: Patient Educ Couns. 2010 Jul;80(1):29-41
references.pmid: 19906503
references.citation: JAMA. 2000 Apr 19;283(15):2008-12
references.pmid: 10789670
references.citation: Dis Markers. 2006;22(3):167-73
references.pmid: 16788250
references.citation: J Clin Epidemiol. 2012 Mar;65(3):293-300
references.pmid: 21995974
references.citation: Mol Biol Rep. 2013 Apr;40(4):3101-12
references.pmid: 23266668
references.citation: N Engl J Med. 1990 Mar 29;322(13):882-9
references.pmid: 2314422
references.citation: Nat Rev Genet. 2006 Dec;7(12):958-65
references.pmid: 17139327
references.citation: Vasc Med. 2001;6(2):103-8
references.pmid: 11530961
references.citation: Atherosclerosis. 1999 Aug;145(2):315-23
references.pmid: 10488959
references.citation: Thromb Haemost. 2011 Mar;105(3):529-34
references.pmid: 21136016
references.citation: Lancet. 2003 Mar 8;361(9360):865-72
references.pmid: 12642066
references.citation: Circ Res. 2000 Mar 3;86(4):391-5
references.pmid: 10700443
references.citation: Am Heart J. 2006 Sep;152(3):538-42
references.pmid: 16923427
references.citation: J Biol Chem. 1996 Feb 16;271(7):3667-70
references.pmid: 8631978
references.citation: Thromb Res. 2010 May;125(5):e197-201
references.pmid: 20100625
references.citation: PLoS One. 2012;7(12):e53105
references.pmid: 23300871
references.citation: Gene. 2012 May 10;499(1):213-7
references.pmid: 22410402
references.citation: BMJ. 2010 Jan 20;340:b5414
references.pmid: 20089597
references.citation: Lancet. 2009 Mar 28;373(9669):1083-96
references.pmid: 19299006
references.citation: Antioxid Redox Signal. 2002 Aug;4(4):675-80
references.pmid: 12230880
references.citation: Circulation. 2012 Jan 3;125(1):188-97
references.pmid: 22215894
references.citation: Eur J Clin Invest. 1999 Sep;29(9):744-8
references.pmid: 10469162
references.citation: Blood. 2000 Aug 1;96(3):1106-12
references.pmid: 10910929
references.citation: Circ Res. 1994 Jun;74(6):1141-8
references.pmid: 8187280
references.citation: Diabetes Care. 2004 Feb;27(2):303-7
references.pmid: 14747204
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120
references.citation: N Engl J Med. 2002 Dec 12;347(24):1916-23
references.pmid: 12477941