Contribution of CDKAL1 rs7756992 and IGF2BP2 rs4402960 polymorphisms in type 2 diabetes, diabetic complications, obesity risk and hypertension in the Tunisian population

J Diabetes. 2015 Jan;7(1):102-13. doi: 10.1111/1753-0407.12147. Epub 2014 Apr 21.

Abstract

Background: The insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and the cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) identified through genome-wide association (GWA) studies have been shown to be associated with Type 2 diabetes in various ethnic groups. In this study, we investigated the association of the rs7756992 of CDKAL1 and the rs4402960 of IGF2BP2 with Type 2 diabetes, diabetic complications (nephropathy, retinopathy and cardiovascular disease), obesity and hypertension in a Tunisian population.

Methods: A case-control association study including 200 Type 2 diabetes Tunisian patients (World Health Organization criteria) and 208 controls (age ≥40; fasting plasma glucose <6.1 mmol/L; without first degree family history of diabetes) has been performed. Other parameters such as diabetic nephropathy, diabetic retinopathy, cardiovascular disease, overweight/obesity and hypertension have been also collected. Genotyping was performed using TaqMan technology.

Results: A significant association between the rs4402960 and Type 2 diabetes (OR = 1.86, 95% CI = 1.34-2.58, P < 10(-4) ) has been found. Overweight/obese subjects bearing the T-allele have an increased risk to develop Type 2 diabetes (OR = 2.06, 95% CI = 1.40-3.03, P < 10(-4) ). Furthermore, the rs7756992 was found to be associated with the reduced risk of diabetic nephropathy in patients with diabetes (OR = 0.44, 95% CI = 0.27-0.73, P = 0.001).

Conclusions: The present study confirms that the rs4402960 of IGF2BP2 gene is a strong candidate for Type 2 diabetes susceptibility and overweight/obesity risk in the Tunisian population. Interestingly, our data suggest that the rs7756992 of CDKAL1 gene have a protective effect against diabetic nephropathy.

Keywords: CDKAL1; IGF2BP2; Tunisian population; Type 2 diabetes; genetic association; 关键词:CDKAL1 ,遗传相关性,IGF2BP2 ,突尼斯人群,2型糖尿病.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Cyclin-Dependent Kinase 5 / genetics*
  • Diabetes Complications / epidemiology
  • Diabetes Complications / etiology*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / etiology
  • Diabetic Retinopathy / epidemiology
  • Diabetic Retinopathy / etiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / epidemiology
  • Hypertension / etiology*
  • Male
  • Middle Aged
  • Obesity / epidemiology
  • Obesity / etiology*
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • RNA-Binding Proteins / genetics*
  • Tunisia / epidemiology
  • tRNA Methyltransferases

Substances

  • IGF2BP2 protein, human
  • RNA-Binding Proteins
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human