Metabolic syndrome, syndrome X, which is reaching epidemic proportions inpopulation, is a cluster of insulin resistance and/or type-II diabetes mellitus with twoor more of hypertension, dyslipidemia, central obesity and albuminuria in anindividual patient. Genetic predisposition for metabolic syndrome was, to largeextent, believed to be an important aspect in its pathogenesis. The renin-angiotensinsystem (RAS) genes are proposed as important genetic factors for diabeticcomplications. Therefore, the angiotensin converting enzyme (ACE) genepolymorphisms (II, ID or DD), which is an important component of RAS genes, mightbe included in the pathogenesis of metabolic syndrome and is a candidate gene forinvestigation in metabolic syndrome. We aimed to study the possible ACE genotypingplasmaACE activity-metabolic syndrome relationship, and to assess the possible roleof ACE genotyping in the pathogenesis of variable components of metabolicsyndrome. This study is also a trial to take the distribution of ACE-I/D genotypeamong subjects as a possible risk marker for metabolic syndrome. ACE genotypeswere determined by PCR amplification, and plasma ACE activity was measured bycolorimetric method in 100 subjects (40 metabolic syndrome patients diagnosedaccording to WHO criteria, 30 type-II diabetic patients without any other criteria ofmetabolic syndrome, and 30 healthy controls). Insulin resistance was judged byhomeostasis model assessment (HOMA) index after estimation of fasting bloodglucose and plasma insulin. Moreover, HbA1c, plasma lipids including totalcholesterol, 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-obesesubjects. ACE-DD genotype and D-allele were found more frequent among metabolicsyndrome patients (Odds ratios were1.25 and 1.16 respectively) and among type-IIdiabetics (Odds ratios were1.25 and 1.10 respectively) than among healthy controls;and more frequent among metabolic syndrome patients than among type-II diabeticpatients (Odds ratios were 1.10 and 1.32 respectively). The plasma ACE activity wasfound significantly higher in patient's groups compared to healthy subjects and inmetabolic patients compared to diabetics. Also, it was significantly and positivelycorrelated to HOMA index in both metabolic syndrome and diabetic patients. Theplasma ACE also in overall studied subjects had direct significant correlation withFBG, 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 groupsDD genotype subgroups had a statistically significant increase in plasma ACEactivity, FBG, HbA1c, plasma insulin, HOMA, total cholesterol, LDL-c, andtriglycerides and a significant decrease in HDL-c and APO-A compared to IIgenotype subjects. Lastly, the ACE-DD genotype was associated with hypertensionand with microalbuminuria than any of II genotype (Odds ratios were 3.50 and 6respectively) and ID genotype (Odds ratios were 2.33 and 1.29 respectively); but notassociated with obesity.In conclusion, ACE Deletion Polymorphism; DD genotype was associated withmetabolic syndrome and type-II diabetes mellitus as well as with obvious increase inplasma ACE activity. All components of metabolic syndrome, except obesity weremore aggressive when the ACE genotype was DD. Therefore, ACE may be a stronggenetic risk factor that is involved in the pathogenesis of metabolic syndrome withtype-II diabetes. Moreover, by detection of DD genotype, we can predict the higherpossibility of occurrence of metabolic complications in type-II diabetics in the futureand suggest early interventions to delay or prevent these complications.