HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bacci, S. Articles by Trischitta, V. Search for Related Content PubMed PubMed Citation Articles by Bacci, S. Articles by Trischitta, V. Social Bookmarking                What's this?

The K121Q Polymorphism of the ENPP1/PC-1 Gene Is Associated With Insulin Resistance/Atherogenic Phenotypes, Including Earlier Onset of Type 2 Diabetes and Myocardial Infarction

¹ Unit of Endocrinology, CSS Scientific Institute, San Giovanni Rotondo, Italy
² CSS-Mendel Institute, Rome, Italy
³ Research Division, Joslin Diabetes Center and the Departments of Medicine, Harvard Medical School, Boston, Massachusetts
⁴ Unit of Cardiology, CSS Scientific Institute, San Giovanni Rotondo, Italy
⁵ Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro, Italy
⁶ Department of Clinical Sciences, University La Sapienza, Rome, Italy

Insulin resistance (IR) is pathogenic for type 2 diabetes and coronary artery disease (CAD). The K121Q polymorphism of the ENPP1/PC-1 gene is associated with IR. Our aim was to investigate the role of the 121Q variant on the risk of type 2 diabetes and CAD. Nondiabetic control subjects (n = 638), type 2 diabetic patients without CAD (n = 535), and type 2 diabetic patients with CAD (n = 434) from Italy and the U.S. were studied. The proportion of 121Q carriers progressively increased in the three groups (27.4, 28.8, and 33.2%, respectively; adjusted P value = 0.027). Among diabetic patients (n = 969), 121Q carriers had an increased risk of developing type 2 diabetes before the age of 65 years (adjusted odds ratio [OR] 2.26, 95% CI 1.26–4.03; P = 0.006) and having a myocardial infarction (MI) (n = 156) by 50 years of age (3.17, 1.46–6.88, P = 0.007). The 121Q variant was also associated with an increased risk for CAD (1.47, 1.01–2.18; P = 0.049) in diabetic patients who did not smoke (n = 546). In conclusion, the ENPP1/PC-1 121Q variant is associated with a progressive deterioration of the IR-atherogenic phenotype; among diabetic individuals, it is also associated with earlier onset of type 2 diabetes and MI.

Abbreviations: CAD, coronary artery disease; FP, fluorescence polarization; IR, insulin resistance; MI, myocardial infarction; OR, odds ratio

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. S. Stolerman, A. K. Manning, J. B. McAteer, J. Dupuis, C. S. Fox, L. A. Cupples, J. B. Meigs, and J. C. Florez Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study Diabetes, July 1, 2008; 57(7): 1971 - 1977. [Abstract] [Full Text] [PDF]

				J. B. McAteer, S. Prudente, S. Bacci, H. N. Lyon, J. N. Hirschhorn, V. Trischitta, J. C. Florez, and for the ENPP1 Consortium The ENPP1 K121Q Polymorphism Is Associated With Type 2 Diabetes in European Populations: Evidence From an Updated Meta-Analysis in 42,042 Subjects Diabetes, April 1, 2008; 57(4): 1125 - 1130. [Abstract] [Full Text] [PDF]

				P. Eller, K. Hochegger, G. M. Feuchtner, E. Zitt, I. Tancevski, A. Ritsch, F. Kronenberg, A. R. Rosenkranz, J. R. Patsch, and G. Mayer Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure Nephrol. Dial. Transplant., September 10, 2007; (2007) gfm566v1. [Abstract] [Full Text] [PDF]

				W. Boonyasrisawat, D. Eberle, S. Bacci, Y.-Y. Zhang, D. Nolan, E. V. Gervino, M. T. Johnstone, V. Trischitta, S. E. Shoelson, and A. Doria Tag Polymorphisms at the A20 (TNFAIP3) Locus Are Associated With Lower Gene Expression and Increased Risk of Coronary Artery Disease in Type 2 Diabetes Diabetes, February 1, 2007; 56(2): 499 - 505. [Abstract] [Full Text] [PDF]

				C. J. Willer, L. L. Bonnycastle, K. N. Conneely, W. L. Duren, A. U. Jackson, L. J. Scott, N. Narisu, P. S. Chines, A. Skol, H. M. Stringham, et al. Screening of 134 Single Nucleotide Polymorphisms (SNPs) Previously Associated With Type 2 Diabetes Replicates Association With 12 SNPs in Nine Genes Diabetes, January 1, 2007; 56(1): 256 - 264. [Abstract] [Full Text] [PDF]

				S. Prudente and V. Trischitta The Pleiotropic Effect of the ENPP1 (PC-1) Gene on Insulin Resistance, Obesity, and Type 2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4767 - 4768. [Full Text] [PDF]

				Y. Bottcher, A. Korner, T. Reinehr, B. Enigk, W. Kiess, M. Stumvoll, and P. Kovacs ENPP1 Variants and Haplotypes Predispose to Early Onset Obesity and Impaired Glucose and Insulin Metabolism in German Obese Children J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4948 - 4952. [Abstract] [Full Text] [PDF]

				M. N. Weedon, B. Shields, G. Hitman, M. Walker, M. I. McCarthy, A. T. Hattersley, and T. M. Frayling No Evidence of Association of ENPP1 Variants With Type 2 Diabetes or Obesity in a Study of 8,089 U.K. Caucasians Diabetes, November 1, 2006; 55(11): 3175 - 3179. [Abstract] [Full Text] [PDF]

				H. N. Lyon, J. C. Florez, T. Bersaglieri, R. Saxena, W. Winckler, P. Almgren, U. Lindblad, T. Tuomi, D. Gaudet, X. Zhu, et al. Common Variants in the ENPP1 Gene Are Not Reproducibly Associated With Diabetes or Obesity Diabetes, November 1, 2006; 55(11): 3180 - 3184. [Abstract] [Full Text] [PDF]

				H. Freeman and R.D. Cox Type-2 diabetes: a cocktail of genetic discovery Hum. Mol. Genet., October 15, 2006; 15(suppl_2): R202 - R209. [Abstract] [Full Text] [PDF]

				T. Soccio, Y.-Y. Zhang, S. Bacci, W. Mlynarski, G. Placha, G. Raggio, R. Di Paola, A. Marucci, M. T. Johnstone, E. V. Gervino, et al. Common Haplotypes at the Adiponectin Receptor 1 (ADIPOR1) Locus Are Associated With Increased Risk of Coronary Artery Disease in Type 2 Diabetes. Diabetes, October 1, 2006; 55(10): 2763 - 2770. [Abstract] [Full Text] [PDF]

				R. Di Paola, E. Ciociola, W. Boonyasrisawat, D. Nolan, J. Duffy, G. Miscio, C. Cisternino, G. Fini, V. Tassi, A. Doria, et al. Association of hGrb10 Genetic Variations With Type 2 Diabetes in Caucasian Subjects Diabetes Care, May 1, 2006; 29(5): 1181 - 1183. [Full Text] [PDF]