Relations between deletion polymorphism of the angiotensin-converting enzyme gene and insulin resistance, glucose intolerance, hyperinsulinemia, and dyslipidemia.
Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. The present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk factors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance and 57 with noninsulin-dependent-diabetes mellitus (NIDDM), and compared various aspects of glucose, insulin, and lipoprotein metabolism in the three ACE genotypes. In general, normal subjects with the DD genotype had a lower body mass index, were more insulin sensitive (as assessed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride and cholesterol concentrations were lowest and HDL cholesterol concentrations highest in the DD group. However, the only statistically significant differences were between the ID and DD groups; the latter had lower values for body mass index, was more insulin sensitive, and had a lower plasma insulin response to oral glucose. Similar but insignificant trends were noted in the patients with NIDDM. The present results show that subjects with the ACE/DD genotype are not at increased risk for CHD because of insulin resistance, relative hyperglycemia and hyperinsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Katsuya
T
T
Falk Cardiovascular Research Center, Stanford Univesity School of Medicine, Calif, USA.
Horiuchi
M
M
Chen
Y D
YD
Koike
G
G
Pratt
R E
RE
Dzau
V J
VJ
Reaven
G M
GM
D001483:Base Sequence; D015992:Body Mass Index; D003327:Coronary Disease / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D007328:Insulin; D007703:Peptidyl-Dipeptidase A