Effect of ENPP1/PC-1-K121Q and PPARg-Pro12Ala polymorphisms on the genetic susceptibility to T2D in the Tunisian population R. Bouhaha a, *, D. Meyre c , H. Abid Kamoun b , H. Ennafaa a , E. Vaillant c , R. Sassi a , T. Baroudi a , V. Vatin c , P. Froguel c,d , A. Elgaaied a , M. Vaxillaire c a Laboratory of Genetics, Immunology and Human Pathologies, Faculty of Sciences of Tunis, 2092 Tunis, Tunisia b Hospital of Charles Nicolle in Tunis, Tunisia c CNRS-8090 and Institute of Biology, Lille 2 University, Pasteur Institute, Lille, France d Genomic Medicine, Hammersmith Hospital, Imperial College London, United Kingdom 1. Introduction Type 2 diabetes mellitus (T2D) is a heterogeneous metabolic disease whose worldwide morbidity and mortality rates are substantially increasing. At least 1 in 10 people alive today will develop diabetes at some point during lifetime. T2D affects more than 200 million people worldwide, and is scheduled to double in the coming generations [1], with increased risk of vascular diseases that result from chronically disturbed glucose metabolism. Concurrently to this increase the occurrence of T2D reaches 9.5% of women and 8.8% of men in the Tunisian population [2]. T2D, like other complex diseases, results from many genes interacting with environmental factors, mainly physical activity, dietary and lifestyle conditions, and also with increasing obesity and ageing [3]. According to World Health Organization more than 1 billion adults are overweighted and at least 300 million of them are clinically obese. In Tunisia, the diabetes research and clinical practice 81 (2008) 278–283 article info Article history: Received 12 February 2008 Received in revised form 11 June 2008 Accepted 12 June 2008 Published on line 25 July 2008 Keywords: ENPP1 PPARg Diabetes Overweight Tunisians abstract Diabetes mellitus is the most common chronic metabolic disease. The raising diabetes epidemic is unfolding as an interaction between several environmental factors and a genetic predisposition. The aim of the current study was to evaluate the role of the PPARg-Pro12Ala and ENPP1-K121Q polymorphisms on type 2 diabetes (T2D) risk in a case–control study in the Tunisian population. To assess for any association of ENPP1-K121Q and PPARg-Pro12Ala polymorphisms with T2D risk, we analysed the genotypic and allelic distributions of each variant in the studied cohort. Our results support that the genetic variation at ENPP1-K121Q predisposes to T2D in the Tunisian population after adjustment on gender, age and BMI status (OR = 1.55, 95%CI [1.11–2.16], p = 0.007). Conversely, the PPARg-Pro12Ala variant seems not to have a significant effect on T2D risk in our Tunisian cohort. However, the minor A-allele would convey protection against overweight in the Tunisian population. In fact, the over weighted subjects showed a significantly lower frequency of A-allele than lean controls (OR = 0.49, 95%CI [0.25–0.97], p = 0.02). In conclusion, our findings support the hypothesis that ENPP1-121Q is involved in the genetic susceptibility of T2D in the Tunisian population, while the PPARg-12Ala allele may confer protection against overweight. # 2008 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +216 25 450 590; fax: +216 71 885 480. E-mail address: rymab12@yahoo.fr (R. Bouhaha). available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2008.06.004