ENPP1/PC-1 K121Q Polymorphism and Genetic Susceptibility to Type 2 Diabetes

  1. Nicola Abate1,
  2. Manisha Chandalia1,
  3. Pankaj Satija1,
  4. Beverley Adams-Huet2,
  5. Scott M. Grundy1,
  6. Sreedharan Sandeep3,
  7. Venkatesan Radha3,
  8. Raj Deepa3 and
  9. Viswanathan Mohan3
  1. 1Department of Medicine, Division of Endocrinology and Metabolism and the Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
  2. 2Center for Biostatistics and Clinical Science, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
  3. 3M.V. Diabetes Specialties Centre and Madras Diabetes Research Foundation, Gopalapuram, Chennai, India
  1. Address correspondence and reprint requests to Nicola Abate, MD, UT Southwestern Medical Center, 6011 Harry Hines Blvd., Dallas, Texas 75390-9169. E-mail: nicola.abate{at}utsouthwestern.edu

Abstract

Genetic susceptibility modulates the impact of obesity on risk for type 2 diabetes. The present study evaluates the role of ENPP1 K121Q polymorphism in prediction of type 2 diabetes in three populations that differ in susceptibility to diabetes and environmental exposure. The three cohorts included 679 nonmigrant South Asians living in Chennai, India (223 with type 2 diabetes); 1,083 migrant South Asians living in Dallas, Texas (121 with type 2 diabetes); and 858 nonmigrant Caucasians living in Dallas, Texas (141 with type 2 diabetes). Patients with type 2 diabetes were included in these cohorts if they had diabetes onset before the age of 60 years. The prevalence of subjects carrying the polymorphic ENPP1 121Q allele was 25% in the nondiabetic group and 34% in the diabetic group of South Asians living in Chennai (P = 0.01). The prevalence in the nondiabetic and diabetic groups were 33 and 45% (P = 0.01) for the South Asians living in Dallas and 26 and 39% (P = 0.003) for the Caucasians. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians.

Footnotes

  • N.A. and M.C. contributed equally to this work.

    • Accepted December 16, 2004.
    • Received July 30, 2004.
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  1. doi: 10.2337/diabetes.54.4.1207 Diabetes April 2005 vol. 54 no. 4 1207-1213
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