English abstract
Type 2 diabetes mellitus (T2DM) is considered as a major health problem in Oman due to relatively high prevalence (16.1%). The peroxisome proliferator activated receptor y2 (PPAR y2) was recently identified as one of the major determinants for T2DM. In this context, the aim of this study was to assess the association between PPARY-2 C34G single nucleotide polymorphisms (SNP) and T2DM or relevant risk factors such as insulin resistance and obesity by applying a new methodology for the detection of these SNPs of the PPARY-2 in Oman. This methodology, known as the Real Time Polymerase Chain Reaction - the Allelic Discrimination assay, is robotic i.e. it can genotype 96 samples in one run which can be useful in genotyping large number of samples in less time. The study population consisted of 330 individuals from an Omani family pedigree which is predicted to provide a strong statistical power to check for segregation the variants of PPARY2 and phenotypes. Furthermore, the population sample had been anthropometrically and biochemically well characterized for diabetes and its components. Anthropometric parameters included body mass index, height, weight, fat content and waist circumference; biochemical parameters included fasting plasma glucose concentrations and concentration two hours after an oral glucose tolerance test, triglycerides, fasting insulin concentrations, HbA1c, and high and low density lipoprotein- cholesterol. Frequency of the CC genotype of the C34G SNP of PPARY-2 was 92.4% and frequency of the CG genotype was 7.3%. C-allele frequency was 0.962 and G-allele frequency was 0.038 which was in Hardy-Weinberg equilibrium. This finding may indicate that the G34-allele frequency in the Omani population is also likely to be 0.038 as detected in the above mentioned sample population. The CG genotype frequency was higher in normoglycemic (7.4%) compared with subjects with impaired glucose homeostasis (IGH) and Type 2 diabetes mellitus (T2DM) (5.3%), however, the difference was not significant at 95% confidence interval. HDL cholesterol levels were significantly higher among CG carriers in the IGH & T2DM group (p = 0.04) compared with CC carriers of the same group, however, this association was lost when regression analysis was carried out with adjusted age, sex and BMI mainly due to BMI. Among the same group, LDL-cholesterol levels remained significantly higher (p = 0.02) among the CG compared with CC carriers even after BMI, sex and age were adjusted. In contrast, Triglyceride (TG) levels were significantly lower (p = 0.04) among the CG carriers compared with CC in the IGH & T2DM group, however, this association was lost when regression analysis with adjusted sex, age and BMI was carried out. Rest of the metabolic parameters showed no statisically significant difference in their mean and median values among CG carriers compared with CC carriers in the normoglycemc and IGH & T2DM group. Despite the absence of significant association between C34G SNP of PPARY2 and T2DM-related traits, some consistent findings with published data were observed. For example, markers of obesity such as BMI, fat content and waist circumference all showed a slightly higher mean levels in CG carriers of both the normoglycemc and IGH & T2DM groups compared with CC carriers indicating that these individuals were likely to develop obesity. Generally, Insulin senstivity measured by Quantitative Insulin Sensitivity Check Index (QUICKI) had shown highr levels among CG carriers compared with CC. To further confirm these results it was recommended to conduct the study on a larger sample size and use the statistically powerful Transmission Disequilibrium Test (TDT) to provide a better estimate of the statistical significance,
