The relationship between the insertion/deletion polymorphism of the ACE gene and hypertension in Iranian patients with type 2 diabetes.
BACKGROUND
Observations on the association between the ACE gene polymorphism and hypertension have been inconsistent, which might be due to ethnic and geographical variations. Moreover, the relationship between insertion/deletion (I/D) polymorphism and hypertension in the diabetic population has not been sufficiently studied. The aim of this study was to evaluate for the first time the possible association between I/D polymorphism and hypertension in an Iranian diabetic adult population.


METHODS
A total of 82 consecutive patients with type 2 diabetes and hypertension (Group A) and 87 patients with type 2 diabetes but without hypertension (Group B) were included. Patients who had a history of hypertension before the onset of diabetes and those with findings suggesting secondary hypertension were excluded. The following variables were determined for each patient: age, sex, body mass index (BMI), diabetes duration and the drugs used, history of coronary artery disease and its complications, blood pressure (systolic and diastolic), fasting blood sugar (FBS), haemoglobin A1c (HbA1c), total cholesterol (Chol), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG), plasma creatinine (Crt) and 24 h urine albumin excretion. Polymerase chain reaction (PCR) was used to detect the I/D alleles. Univariate (chi-squared and t-test) and multivariate (multivariate binary logistic regression with adjusted odds ratios) analyses were applied to determine the association between I/D polymorphism (with genotype II as reference) and hypertension. P<0.05 was considered statistically significant.


RESULTS
In univariate analysis, the groups were statistically similar in all variables except for diabetes duration (156.05+/-73.54 months in Group A vs 121.74+/-65.53 months in Group B; P=0.002), Crt (1.04+/-0.25 mg/dl in Group A vs 0.93+/-0.23 mg/dl in Group B; P=0.003), albuminuria (486.25+/-484.60 mg/d in Group A vs 316.50+/-459.56 mg/d in Group B; P=0.021) and the frequency of DD genotype (27 cases in Group A vs 11 cases in Group B; P=0.026). Multivariate logistic regression (using age, sex and BMI as clinically significant variables and diabetes duration, Crt, albuminuria and genotype as statistically significant variables) was then used to determine independent associations and adjusted odds ratios (OR). The DD genotype was the strongest independent predictor of hypertension [P=0.029, OR=3.122, 95% confidence interval (CI)=1.127-8.647], followed by log (albuminuria) (P=0.042, OR=1.183, 95% CI=1.006-1.391). Considering albuminuria as a categorical variable did not change the results significantly.


CONCLUSIONS
The DD polymorphism in the ACE gene is independently associated with hypertension in the diabetic population.
Nakhjavani
Manouchehr
M
Endocrine and Metabolism Research Center, Vali-Asr Hospital, and Department of Biochemistry, School of Medicine, Medical Sciences, University of Tehran, No 12, Aramesh Alley, Mellat Park, Tehran, Iran.
Esfahanian
Fatemeh
F
Jahanshahi
Alireza
A
Esteghamati
Alireza
A
Nikzamir
Abdol Rahim
AR
Rashidi
Armin
A
Zahraei
Mahin
M
D000419:Albuminuria; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000235:genetics*; D007492:Iran; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A