Association of angiotensin II type 1 receptor gene A1166C polymorphism with the presence of diabetes mellitus and metabolic syndrome in patients with documented coronary artery disease.

BACKGROUND: There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients. METHODS: Patients with angiographically defined coronary artery disease (CAD) (n=309) were evaluated for the presence of AT(1)R/A1166C polymorphism. These patients were classified into subgroups with (n=164, M/F: 109/55) and without (n=145, M/F: 84/61) diabetes mellitus. The AT(1)R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method. RESULTS: There was a higher frequency of polymorphic genotypes (AC+CC) in the diabetic compared with the non-diabetic group (p=0.01). When determined for each gender separately, this difference remained significant in the males (p=0.04) but not in females (p=0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p=0.01). This remained significant after gender segregation for males (p=0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (ß=1.16, p<0.001 for total population and ß=1.29, p<0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p=0.04). CONCLUSION: The AT(1)R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD.

Association between 45T/G polymorphism of adiponectin gene and coronary artery disease in an Iranian population.

A single nucleotide polymorphism (SNP) in the adiponectin gene, 45T/G, has been reported in relation to a number of metabolic disorders, including obesity, insulin resistance, and diabetes. However, previous studies on the association between this SNP and the presence of coronary artery disease (CAD) have been few, with no report from Iranian subjects. The present study set out to investigate the association between this SNP and CAD in an Iranian population. Among 464 patients (age: 18-75 years), recruited from individuals who underwent coronary angiography, 135 patients had less than 50% reduction of coronary artery diameter and were classified as the CAD- group and 329 patients had more than 50% reduction of coronary artery diameter and were classified as the CAD+ group. The last group was divided into single-vessel disease (n = 86), two-vessel disease (n = 111), and three-vessel disease (n = 132). Healthy subjects (n = 106) who did not have any history of heart diseases were also recruited as the control group. All subjects were genotyped for the 45T/G polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. A significantly higher frequency of the TG genotype and G allele, which was paralleled by a lower frequency of the TT genotype and T allele, was observed in both CAD+ and CAD- patients when compared with the control group (p ≤ 0.001). There was no significant difference in the genotype distribution and allele frequencies between CAD+ and CAD- patients, and also between different subgroups of patients based on the number of stenosed vessels (p > 0.05). Our findings indicate that the presence of the G allele at the position +45 of the adiponectin gene may be associated with the risk of CAD in our study population. While we found no significant difference in the genotype distribution and allele frequencies between patients with angiography+ and angiography, this may be because the 50% stenosis cut-off does not discriminate sufficiently between individuals with and without significant coronary disease.