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

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  • Additional Information
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
    • Publication Information:
      Publication: Alexandria, VA : American Diabetes Association
      Original Publication: [New York, American Diabetes Association]
    • Subject Terms:
      Cardiovascular Diseases/*epidemiology ; Cardiovascular Diseases/*genetics ; Diabetes Mellitus, Type 2/*genetics ; Obesity/*genetics ; Phosphoric Diester Hydrolases/*genetics ; Pyrophosphatases/*genetics; Aged ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Genetic Association Studies ; Genotype ; Humans ; Incidence ; Italy ; Male ; Middle Aged ; Obesity/epidemiology ; Polymorphism, Genetic ; Prospective Studies ; Risk Factors ; Statistics, Nonparametric ; White People/genetics
    • 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.
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    • Grant Information:
      P30 DK036836 United States DK NIDDK NIH HHS; R01 HL073168-08 United States HL NHLBI NIH HHS; DK36836 United States DK NIDDK NIH HHS; R01 HL073168 United States HL NHLBI NIH HHS; HL73168 United States HL NHLBI NIH HHS
    • Accession Number:
      EC 3.1.4.- (Phosphoric Diester Hydrolases)
      EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
      EC 3.6.1.- (Pyrophosphatases)
    • Publication Date:
      Date Created: 20110202 Date Completed: 20110422 Latest Revision: 20221207
    • Publication Date:
      20231215
    • Accession Number:
      PMC3046818
    • Accession Number:
      10.2337/db10-1300
    • Accession Number:
      21282363