TY - JOUR
T1 - The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk
T2 - Two case-control studies and a meta-analysis
AU - Di Castelnuovo, Augusto
AU - Soccio, Manola
AU - Iacoviello, Licia
AU - Evangelista, Virgilio
AU - Consoli, Agostino
AU - Vanuzzo, Diego
AU - Diviacco, Silvia
AU - Carluccio, Marisa
AU - Rignanese, Lucia
AU - De Caterina, Raffaele
PY - 2008/3
Y1 - 2008/3
N2 - 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 C242T 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 casecontrol 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 metaanalyzed together with additional studies retrieved from the literature. The C242T 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 metaanalysis, 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 C242T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.
AB - 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 C242T 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 casecontrol 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 metaanalyzed together with additional studies retrieved from the literature. The C242T 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 metaanalysis, 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 C242T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.
KW - Gene polymorphisms
KW - Meta-analysis
KW - NADPH oxidase
KW - p22-phox
KW - Reactive oxygen species
KW - Vascular risk
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U2 - 10.1160/TH07-08-0480
DO - 10.1160/TH07-08-0480
M3 - Article
C2 - 18327409
AN - SCOPUS:42249115247
VL - 99
SP - 594
EP - 601
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
SN - 0340-6245
IS - 3
ER -