The \(ENPP1\) Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals

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The \(ENPP1\) Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals

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dc.contributor.author Bacci, Simonetta
dc.contributor.author Rizza, Stefano
dc.contributor.author Prudente, Sabrina
dc.contributor.author Spoto, Belinda
dc.contributor.author Powers, Christine
dc.contributor.author Facciorusso, Antonio
dc.contributor.author Pacilli, Antonio
dc.contributor.author Lauro, Davide
dc.contributor.author Testa, Alessandra
dc.contributor.author Zhang, Yuan-Yuan
dc.contributor.author Di Stolfo, Giuseppe
dc.contributor.author Mallamaci, Francesca
dc.contributor.author Tripepi, Giovanni
dc.contributor.author Xu, Rui
dc.contributor.author Mangiacotti, Davide
dc.contributor.author Aucella, Filippo
dc.contributor.author Lauro, Renato
dc.contributor.author Copetti, Massimiliano
dc.contributor.author De Cosmo, Salvatore
dc.contributor.author Pellegrini, Fabio
dc.contributor.author Zoccali, Carmine
dc.contributor.author Federici, Massimo
dc.contributor.author Trischitta, Vincenzo
dc.contributor.author Gervino, Ernest Vincent
dc.contributor.author Hauser, Thomas Henry
dc.contributor.author Doria, Alessandro
dc.date.accessioned 2012-08-10T18:08:36Z
dc.date.issued 2011
dc.identifier.citation Bacci, Simonetta, Stefano Rizza, Sabrina Prudente, Belinda Spoto, Christine Powers, Antonio Facciorusso, Antonio Pacilli, et al. 2011. The \(EMPP1\) Q121 variant predicts major cardiovascular events in high-risk individuals. Diabetes 60(3): 1000-1007. en_US
dc.identifier.issn 0012-1797 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9393252
dc.description.abstract OBJECTIVE: Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated \(ENPP1\) K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals. RESEARCH DESIGN AND METHODS: A prospective study (average follow-up, 37 months) was conducted for major cardiovascular events (myocardial infarction [MI], stroke, cardiovascular death) from the Gargano Heart Study (GHS; \(n\) = 330 with type 2 diabetes and coronary artery disease), the Tor Vergata Atherosclerosis Study (TVAS; \(n\) = 141 who had MI), and the Cardiovascular Risk Extended Evaluation in Dialysis (CREED) database (\(n\) = 266 with end-stage renal disease). Age at MI was investigated in cross-sectional studies of 339 type 2 diabetic patients (\(n\) = 169 from Italy, n = 170 from the U.S.). RESULTS: Incidence of cardiovascular events per 100 person--years was 4.2 in GHS, 10.8 in TVAS, and 11.7 in CREED. Hazard ratios (HRs) for KQ+QQ versus individuals carrying the K121/K121 genotype (KK) individuals were 1.47 (95% CI 0.80–2.70) in GHS, 2.31 (95% CI 1.22–4.34) in TVAS, and 1.36 (95% CI 0.88–2.10) in CREED, and 1.56 (95% CI 1.15–2.12) in the three cohorts combined. In the 395 diabetic patients, the Q121 variant predicted cardiovascular events among obese but not among nonobese individuals (HR 5.94 vs. 0.62, \(P\) = 0.003 for interaction). A similar synergism was observed in cross-sectional studies, with age at MI being 3 years younger in Q121 carriers than in KK homozygotes among obese but not among nonobese patients (\(P\) = 0.035 for interaction). CONCLUSIONS: The \(ENPP1\) K121Q polymorphism is an independent predictor of major cardiovascular events in high-risk individuals. In type 2 diabetes, this effect is exacerbated by obesity. Future larger studies are needed to confirm our finding. en_US
dc.language.iso en_US en_US
dc.publisher American Diabetes Association en_US
dc.relation.isversionof doi:10.2337/db10-1300 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046818/pdf/ en_US
dash.license LAA
dc.title The \(ENPP1\) Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Diabetes en_US
dash.depositing.author Gervino, Ernest Vincent
dc.date.available 2012-08-10T18:08:36Z

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