RELATIONSHIP OF RAS GENE POLYMORPHISM TO TYPE-II DIABETES AND SYNDROME-X | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 1, Volume 31, Issue 2, June 2011, Page 1-24 PDF (349.81 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2011.36077 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
| Mohammed Fawzy* 1; Ibrahim El-Maghawry1; Nader A1; Eman Abd Elsalam1; Osama Khalil2 | ||||
| 1Medical Biochemistry Department, Faculty of Medicine, Zagazig University | ||||
| 2Internal Medicine Department, Faculty of Medicine, Zagazig University | ||||
| 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, HbA1c, 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, HbA1c, plasma insulin, HOMA index, TC, LDL-c, and TG; and indirect significant 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, HbA1c, 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 with hypertension and with microalbuminuria than any of II genotype (Odds ratios were 3.50 and 6 respectively) and ID genotype (Odds ratios were 2.33 and 1.29 respectively); but not associated with obesity. In conclusion, ACE Deletion Polymorphism; DD genotype was associated with metabolic syndrome and type-II diabetes mellitus as well as with obvious increase in plasma ACE activity. All components of metabolic syndrome, except obesity were more aggressive when the ACE genotype was DD. Therefore, ACE may be a strong genetic risk factor that is involved in the pathogenesis of metabolic syndrome with type-II diabetes. Moreover, by detection of DD genotype, we can predict the higher possibility of occurrence of metabolic complications in type-II diabetics in the future and suggest early interventions to delay or prevent these complications. | ||||
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