The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: Evidence for interaction with obesity in diabetic patients

Simonetta Bacci, Stefano Rizza, Sabrina Prudente, Belinda Spoto, Christine Powers, Antonio Facciorusso, Antonio Pacilli, Davide Lauro, Alessandra Testa, Yuan Yuan Zhang, Giuseppe Di Stolfo, Francesca Mallamaci, Giovanni Tripepi, Rui Xu, Davide Mangiacotti, Filippo Aucella, Renato Lauro, Ernest V. Gervino, Thomas H. Hauser, Massimiliano CopettiSalvatore De Cosmo, Fabio Pellegrini, Carmine Zoccali, Massimo Federici, Alessandro Doria, Vincenzo Trischitta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1000-1007
Number of pages8
JournalDiabetes
Volume60
Issue number3
DOIs
Publication statusPublished - Mar 2011

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Bacci, S., Rizza, S., Prudente, S., Spoto, B., Powers, C., Facciorusso, A., Pacilli, A., Lauro, D., Testa, A., Zhang, Y. Y., Di Stolfo, G., Mallamaci, F., Tripepi, G., Xu, R., Mangiacotti, D., Aucella, F., Lauro, R., Gervino, E. V., Hauser, T. H., ... Trischitta, V. (2011). The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: Evidence for interaction with obesity in diabetic patients. Diabetes, 60(3), 1000-1007. https://doi.org/10.2337/db10-1300