The \(ENPP1\) Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals
Di Stolfo, Giuseppe
De Cosmo, Salvatore
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CitationBacci, 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.
AbstractOBJECTIVE: 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.
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