Angiotensin converting polymorphism in obese patients

ABSTRACT

Obesity is a complex disorder caused by the interaction of environmental and genetic susceptibility associated with increased risk of morbidity from a variety of disorders. The aim of the present study was to investigate the association between ACE I/D polymorphism and obesity and its contribution to the different risk factors among obese patients which may constitute the basis for strategies to manage this serious problem. Fifty-four male obese patients with BMI >/= 30 kg/m[2] were recruited. Twenty-six healthy men with BMI < 25 kg/m[2] of comparable age were selected as a control group. All patients and controls were subjected to thorough history taking, anthropometric measurements [weight, height, BMI, waist and hip circumference and WHR] and BP measurement. ECG was done. Laboratory investigations included FPG, PPPG, HbA[1c], OGTT, lipid profile and fasting serum insulin. IR was determined by the computer updated 1996 version of HOMA2. ACE I/D polymorphism was determined by PCR. Eighteen and a half percent of obese patients had a family history of CHD and 31.5% were smokers. Nineteen patients were categorized as prehypertensives while 20 had stage 1 or stage 2 hypertension. IHD was diagnosed in five obese patients. Hyperlipidemia, IGT and DM were detected in 61.1%, 50% and 22.2% of obese patients, respectively; 29.6% of patients had grade I obesity, 29.6% had grade II and 40.7% had grade III obesity. Sixty-three percent of patients had a waist circumference> 102 cm and 38.9% had a WHR> 1.0. Obese patients had significantly higher FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR and HOMA2-%B as compared to controls. On the other hand, HOMA2-% S was significantly lower in obese patients. All studied lipid parameters were significantly higher in obese patients except HDL-cholesterol which was significantly lower in obese patients. The distribution of the ACE genotype for obese patients was 38.9%, 46.3% and 14.8%, for the DD, ID and II, respectively. In controls, 34.6% were DD, 46.2% were ID and 19.2% were II genotype. There was no statistically significant difference between obese patients and controls as regards the genotype frequency [Pearson X[2]=0.296; P=0.862]. Relative allele frequencies in both groups were D allele 0.620 in obese versus 0.577 in controls and I allele 0.380 versus 0.423, respectively with no statistically significant difference as well. There was a statistically significant difference between the three ACE I/D genotypes of obese patients as regards BMI, waist circumference and WHR. The DD genotype was associated with higher values of these obesity markers. No such differences were observed for control participants. There were no significant differences in age, SBP and DBP among the three ACE genotypes of obese patients. However, there was a tendency towards DD genotype in the older age group and in patients with higher BP. There was no significant difference between DD, ID and II ACE genotypes of obese patients as regards any of the studied metabolic parameters. However, numerically higher values of FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR, serum triglycerides, total cholesterol and LDL-C and lower values of HOMA2-%S and HDL-cholesterol were observed among DD genotypic obese patients. Overall, DD homozygote obese patients showed a tendency for family history of CHD, smoking, abdominal adiposity, hypertension, hyperlipidemia and DM. ACE I/D polymorphism was significantly associated with abdominal adiposity, hyperlipidemia and DM in obese patients when compared with patients having no such risk factors [P=0.021, P=0.049, P=0.045, respectively]. Nine obese patients showed a maximum of five associated risk factors that were added to obesity, while only two obese patients presented with no such associated risk factors at all. Seven of those nine obese patients were DD homozygotes. It was found that the more the number of studied risk factors added to obesity, the more the prevalence of the DD homozygote genotype [LLR=27.153; P=0.002]. The results of the present study could indirectly suggest that the DD genotype contributes a genetic factor for the development of abdominal obesity and that this would predispose obese patients to further risk for development of CHD. ACE inhibitor therapy can induce improvements in atherosclerosis and IR and therefore they are ideal drugs to be used in obese hypertensive patients