Thromb Haemost 2008; 99(03): 594-601
DOI: 10.1160/TH07-08-0480
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

The C242T polymorphism of the p22phox component of NAD (P)H oxidase and vascular risk

Two case-control studies and a meta-analysis
Augusto Di Castelnuovo
1   Laboratory of Genetic and Environmental Epidemiology, Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Manola Soccio
2   Institute of Cardiology
3   Center of Excellence on Aging, “G. d’Annunzio University”, Chieti, Italy
,
Licia Iacoviello
1   Laboratory of Genetic and Environmental Epidemiology, Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Virgilio Evangelista
4   Consorzio Mario Negri Sud, Santa Maria Imbaro
,
Agostino Consoli
3   Center of Excellence on Aging, “G. d’Annunzio University”, Chieti, Italy
,
Diego Vanuzzo
5   Cardiovascular Prevention Center, ASS 4 and Agenzia Regionale della Sanità del Friuli- Venezia Giulia, Udine
,
Silvia Diviacco
5   Cardiovascular Prevention Center, ASS 4 and Agenzia Regionale della Sanità del Friuli- Venezia Giulia, Udine
,
Marisa Carluccio
6   CNR Institute of Clinical Physiology, Pisa, Italy
,
Lucia Rignanese
2   Institute of Cardiology
3   Center of Excellence on Aging, “G. d’Annunzio University”, Chieti, Italy
,
Raffaele De Caterina
2   Institute of Cardiology
3   Center of Excellence on Aging, “G. d’Annunzio University”, Chieti, Italy
6   CNR Institute of Clinical Physiology, Pisa, Italy
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Publikationsverlauf

Received: 01. August 2007

Accepted after major revision: 16. Januar 2008

Publikationsdatum:
07. Dezember 2017 (online)

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Summary

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 metaanalysis with || 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.