4.5 Article

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

Journal

JOURNAL OF DIABETES
Volume 7, Issue 1, Pages 102-113

Publisher

WILEY
DOI: 10.1111/1753-0407.12147

Keywords

CDKAL1; genetic association; IGF2BP2; Tunisian population; Type 2 diabetes

Funding

  1. NEPAD/NABNet_T2D_NA (New Partnership for Africa's Development, North Africa Biosciences Network, Type 2 diabetes, North Africa)
  2. joint WHO/EMRO-COMSTECH RABGH grants
  3. Tunisian Ministry of Higher Education and Scientific Research
  4. Tunisian Ministry of Health

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BackgroundThe 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. MethodsA case-control association study including 200 Type 2 diabetes Tunisian patients (World Health Organization criteria) and 208 controls (age 40; fasting plasma glucose <6.1mmol/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. ResultsA 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). ConclusionsThe 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.

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