Genetic polymorphisms associated with the development of type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) constitutes a worldwide health problem associated with strong cardiovascular risk. There are environmental factors that contribute for the development of this disease, such as obesity or sedentary life. However, individuals with normal weight can have T2DM and, on the other hand, many of the obese individuals will not develop diabetes, suggesting that it is compelling. the evaluation of other variables, such as genetic factors. Objective: Our study aims to investigate genetic polymorphisms associated with the T2DM onset in a Portuguese population. Methods: We performed a case-control study with 1938 Caucasians which 548 were diabetic type 2 patients (classified as diabetic according to the European Association for the Study of Diabetes) and 1390 were controls, with no significant difference in age. Blood samples for genetic analysis were collected, from both groups, in order to evaluate 18 genetic variants previously described as being associated to hypertension, obesity, diabetes or coronary disease as PON1 Q192R and PON1 L55M, KIF6 T/A, HNF4A C/G, FTO A/C, TAS2R50 A/G, PCSK9 G/A, GJA4 C/T, TCF7L2 C/T, ACE I/D, AGT M235T, AT1R A1166C, MTHFR C677T e MTHFR A1298C, 9P21 locus (rs1333049 G/C) and APOE (ε2, ε3, ε4). Data are presented by mean ± SD. Continuous variables are evaluated by Student t test and categorical variables by Chi Square tests. The power of the association was expressed by the Odds Ratio (OR) and 95% confidence intervals. Multivariate logistic regression is performed to determinate which polymorphic variants were significantly and independently associated with T2DM. A p-value less than 0.05 was considered statistically significant. Results: The polymorphisms that showed association with T2DM, in the univariate analysis were: TCF7L2 TT (OR=1.69; p=0.0002) and AT1R CC (OR=1.58; p=0.021). After logistic regression, with all the genetic variants investigated and the environmental factors, only the TCF7L2 TT (OR=1.99; p<0.0001) remained in the equation showing to be significantly and independently associated with T2DM emergence. Conclusions: This study suggests that there is in our population a genetic polymorphism that independently contributes to the development of T2DM. Since diabetes is associated with a very strong cardiovascular risk, the patients carrying this polymorphism should be approached with early preventive measures, in order to counteract their genetic tendency to develop diabetes.