title: The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis.
abstract: NAD(P)H oxidase is a prominent source of reactive oxygen species in the vasculature. Vascular NAD(P)H oxidase is comprised of several subunits, one of which, p22phox, is encoded by a gene exhibiting several allelic variants. Here the C(242)T nucleotide transition has been found to alter superoxide anion production and associated with an altered risk of coronary artery disease (CAD). We assessed the role of this variant in two case-control studies, and performed a meta-analysis of previously reported investigations relating it to vascular risk. Population I was comprised of 492 subjects with type 2 diabetes, with or without macrovascular disease, matched for age, sex, and duration of diabetes. Population II was comprised of 158 subjects with or without either CAD or cerebro-vascular disease, and matched for age, sex, smoking status, weight category and the presence of hypertension, dyslipidemia, and diabetes. Our findings were meta-analyzed together with additional studies retrieved from the literature. The C(242)T polymorphism distribution did not differ between cases and controls in populations I and II both at univariate and multivariate analyses, and this was confirmed in a meta-analysis with 11 previously published populations. The meta-analysis, however, suggested a protective role of the T allele on CAD as an end point in Asian populations. In conclusion, these data suggest a significant heterogeneity for a modulating role of the T allele in the C(242)T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.
authors.affiliation: Laboratory of Genetic and Environmental Epidemiology, Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Di Castelnuovo
authors.forename: Manola
authors.initials: M
authors.lastname: Soccio
authors.forename: Licia
authors.initials: L
authors.lastname: Iacoviello
authors.forename: Virgilio
authors.initials: V
authors.lastname: Evangelista
authors.forename: Agostino
authors.initials: A
authors.lastname: Consoli
authors.forename: Diego
authors.initials: D
authors.lastname: Vanuzzo
authors.forename: Silvia
authors.initials: S
authors.lastname: Diviacco
authors.forename: Marisa
authors.initials: M
authors.lastname: Carluccio
authors.forename: Lucia
authors.initials: L
authors.lastname: Rignanese
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C086986:CYBA protein, human