TCF7L2 and FTO Polymorphisms Are Associated with Type 2 Diabetes Mellitus Risk in Kuwait

Abstract

<b><i>Objective:</i></b> Despite the high prevalence of type 2 diabetes mellitus (T2DM) and obesity in the region, reports are limited on genetic risk factors associated with T2DM risk in Kuwait. Our aim was to investigate the association of reported <i>FTO</i> and <i>TCF7L2</i> T2DM genetic risk variants in Kuwaiti T2DM patients. <b><i>Subjects and Methods:</i></b> <i>FTO</i> rs9939609 and <i>TCF7L2</i> rs7903146 variants were genotyped in 203 T2DM patients and 162 healthy controls. Data analysis included Fisher’s exact test, χ² test, and linear and logistic regression analyses. <b><i>Results:</i></b> <i>FTO</i> rs9939609 (AA) and <i>TCF7L2</i> rs7903146 (TT) genotypes associated with T2DM risk among Kuwaitis (<i>p</i> = 0.0016 and <i>p</i> &lt; 0.0001; respectively). Both variants had the strongest association with T2DM risk in an autosomal recessive inheritance model (<i>FTO</i> rs9939609A: odds ratio (OR) 2.136, 95% confidence interval (CI): 1.21–3.67, <i>p</i> = 0.0075; <i>TCF7L2</i> rs7903146T: OR 3.283, 95% CI: 1.92–5.76, <i>p</i> &lt; 0.0001). Moreover, rs7903146T associated with risk of peripheral neuropathy (β = 0.735, 95% CI: 0.514–0.96, <i>p</i> &lt; 0.001) and risk of myocardial infarction (β = 0.36, 95% CI: 0.024–0.7, <i>p</i> = 0.036) in T2DM patients. <b><i>Conclusion:</i></b> The increased susceptibility of Kuwaitis to T2DM is influenced by the same common genetic factors found in other T2DM populations. Further investigations of other T2DM genetic risk factors in Kuwait should refine and further support the clinical utility of a genetic risk score in predicting T2DM risk in a high-risk population such as Kuwait.