Candidate Gene Polymorphisms and Risk of Type-2 Diabetes Mellitus in Gaza Strip

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a multifactorial disease that results from the interaction between multiple genetic and environmental factors. Genome-wide association studies revealed many T2DM-associated genetic polymorphisms in various populations. Among the genes polymorphisms that were strongly associated with diabetes are (PPARG rs1801282), (TCF7L2 rs7903146), (SLC30A8 rs13266634), (CDKAL1 rs10946398), and (KCNJ11 E23K). Objective: To investigate the association between (PPARG rs1801282), (TCF7L2 rs7903146), (SLC30A8 rs13266634), (CDKAL1 rs10946398), and (KCNJ11 E23K). genes polymorphisms and T2DM in the Gaza strip population. Methods: In this case-control study 100 T2DM male patients and 100 control men were examined. The two groups were genotyped for the five genes polymorphisms using restriction fragment length polymorphism-PCR (RFLP-PCR) technique. Body mass index (BMI), glycated hemoglobin (HbA1c), insulin (C-peptide), total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were measured for all the study participants. The relation between the five genes polymorphisms, T2DM and the measured clinical parameters were statistically analyzed using appropriate tests. Results: Among the tested polymorphisms, significant association was evident only between KCNJ11 E23K polymorphism and T2DM (P = 0.03). The TCF7L2 "TT" genotype was significantly associated with increased HDL-C levels in both patients and controls (P values = 0.01 and 0.04, respectively). Moreover, the "TT" genotype proved to be significantly associated with lower plasma LDL-C in the patient group (P = 0.001). The SLC30A8 "TT" genotype showed a significant effect on BMI in the control subjects (P value = 0.01) and on lower HbA1c level in the patient group (P value = 0.02). There was a significant increase in the means of BMI, triglycerides and HbA1c in patients as compared to controls (P values = 0.00, 0.02, and 0.00, respectively). Conclusion: KCNJ11 E23K is significantly associated with T2DM in the Gaza strip population. The TCF7L2 "TT" genotype is significantly related to increased HDL-C level in the study population and to lower plasma LDL-C in the patients group. The SLC30A8 "TT" genotype is significantly correlated with BMI in the control group. The means of BMI, triglycerides and HbA1c are significantly increased in patients as compared to controls. The study recommends confirming the obtained results on a larger sample, and examining the association of other genes polymorphisms with T2DM in Gaza strip. Keywords: (PPARG), (TCF7L2), (SLC30A8), (CDKAL1),( KCNJ11 E23K), polymorphism ,type 2 diabetes mellitus, T2DM, Gaza strip.