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

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

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