Relationship of Ras Gene Polymorphism to Type-Ii Diabetes and Syndrome-X

Abstract

Metabolic syndrome, syndrome X, which is reaching epidemic proportions in population, is a cluster of insulin resistance and/or type-II diabetes mellitus with two or more of hypertension, dyslipidemia, central obesity and albuminuria in an individual patient. Genetic predisposition for metabolic syndrome was, to large extent, believed to be an important aspect in its pathogenesis. The renin-angiotensin system (RAS) genes are proposed as important genetic factors for diabetic complications. Therefore, the angiotensin converting enzyme (ACE) gene polymorphisms (II, ID or DD), which is an important component of RAS genes, might be included in the pathogenesis of metabolic syndrome and is a candidate gene for investigation in metabolic syndrome. We aimed to study the possible ACE genotypingplasma ACE activity-metabolic syndrome relationship, and to assess the possible role of ACE genotyping in the pathogenesis of variable components of metabolic syndrome. This study is also a trial to take the distribution of ACE-I/D genotype among subjects as a possible risk marker for metabolic syndrome. ACE genotypes were determined by PCR amplification, and plasma ACE activity was measured by colorimetric method in 100 subjects (40 metabolic syndrome patients diagnosed according to WHO criteria, 30 type-II diabetic patients without any other criteria of metabolic syndrome, and 30 healthy controls). Insulin resistance was judged by homeostasis model assessment (HOMA) index after estimation of fasting blood glucose and plasma insulin. Moreover, HbA 1c , plasma lipids including total cholesterol, LDL-c, HDL-c, triglycerides and APO-A were assessed. Microalbuminuria was determined by dipstick method. The indices body mass index (BMI) and waist:hip ratio (WHR) were used to differentiate obese from non-obese subjects. ACE-DD genotype and D-allele were found more frequent among metabolic syndrome patients (Odds ratios were1.25 and 1.16 respectively) and among type-II diabetics (Odds ratios were1.25 and 1.10 respectively) than among healthy controls; and more frequent among metabolic syndrome patients than among type-II diabetic patients (Odds ratios were 1.10 and 1.32 respectively). The plasma ACE activity was found significantly higher in patient's groups compared to healthy subjects and in metabolic patients compared to diabetics. Also, it was significantly and positively correlated to HOMA index in both metabolic syndrome and diabetic patients. The plasma ACE also in overall studied subjects had direct significant correlation with FBG, HbA 1c , plasma insulin, HOMA index, TC, LDL-c, and TG; and indirect Bull. Egypt. Soc. Physiol. Sci. 31 (2) 2011 Fawzy et al. 2significant correlation with HDL-c and APO-A. Moreover, in the three studied groups DD genotype subgroups had a statistically significant increase in plasma ACE activity, FBG, HbA 1c , plasma insulin, HOMA, total cholesterol, LDL-c, and triglycerides and a significant decrease in HDL-c and APO-A compared to II genotype subjects. Lastly, the ACE-DD genotype was associated wit...