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- Title
The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals.
- Authors
Bacci, Simonetta; Rizza, Stefano; Prudente, Sabrina; Spoto, Belinda; Powers, Christine; Facciorusso, Antonio; Pacilli, Antonio; Lauro, Davide; Testa, Alessandra; Yuan-Yuan Zhang; Di Stolfo, Giuseppe; Mallamaci, Francesca; Tripepi, Giovanni; Rui Xu; Mangiacotti, Davide; Aucella, Filippo; Lauro, Renato; Gervino, Ernest V.; Hauser, Thomas H.; Copetti, Massimiliano
- 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 Tot 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.
- Subjects
INSULIN resistance; CARDIOVASCULAR diseases risk factors; TYPE 2 diabetes; OBESITY; PEOPLE with diabetes
- Publication
Diabetes, 2011, Vol 60, Issue 3, p1000
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db10-1300