The I/D polymorphism of angiotensin-converting enzyme gene but not the angiotensinogen gene is associated with insulin response to oral glucose in Japanese.

Polymorphisms of angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) genes have been reported to be associated with myocardial infarction and coronary artery disease, both of which are closely related to atherosclerosis and insulin resistance. In this study, we investigated the association between ACE and AGT genotypes and insulin sensitivity in a sample of 142 nondiabetic and 64 noninsulin-dependent diabetes mellitus (NIDDM) Japanese subjects, aged 62.7 +/- 9.5 years. The insulin response to the 75-g oral glucose tolerance test (OGTT) was significantly lower in subjects with the ACE D/D genotype compared to those with the I allele (I/D and I/I genotypes) in both nondiabetic (P < 0.05) and NIDDM subjects (P < 0.005). These homozygous D/D subjects also had lower insulin area under the curve of plasma insulin concentrations during OGTT compared to those with the I allele in nondiabetic (P < 0.05) and NIDDM subjects (P < 0.01). However, there was no significant association between AGT genotypes and either insulin response or insulin area under the curve during OGTT, in either nondiabetic or NIDDM subjects. From a viewpoint that insulin response to oral glucose is significantly correlated with insulin sensitivity, these results suggest that polymorphic variations at the ACE gene, but not the AGT gene, may be involved in the genetic regulation of insulin sensitivity in both nondiabetic and NIDDM Japanese subjects.

A polymorphism of angiotensinogen gene codon 174 and coronary artery disease in Japanese subjects.

The relationship between coronary artery disease (CAD) and polymorphisms of genes encoding angiotensinogen (AGT) and angiotensin converting enzyme (ACE) was analyzed in Japanese subjects. One hundred and four patients with CAD and 170 healthy subjects were enrolled in the study. CAD was defined as having a luminal diameter stenosis > or =50% in at least one of three major coronary arteries by coronary angiography. The genotypes (determined by polymerase chain reaction) of AGT gene codon 174 were not significantly associated with CAD in the total study population. However, the frequency of T/T homozygotes of AGT codon 174 was significantly higher in CAD patients compared to controls in each of three subgroups: 1) body mass index (BMI) below the median value of 24.1 kg/m2; 2) not more than two CAD risk factors out of five (hypercholesterolemia, hypertension, diabetes mellitus, smoking, and family history of CAD); and 3) the ACE I/I genotype. The M/M genotype of AGT codon 235 was negatively associated, and the ACE D/D genotype was positively associated, with CAD in the total study population. Our results indicate that the T/T genotype of AGT codon 174 may be a risk factor for CAD in Japanese individuals with low BMI, lesser CAD risk factors, or ACE I/I genotype.