Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart disease

Polymorphisms of the angiotensin-converting enzyme (ACE) (insertion/deletio n (I/D) in intron 16) and of the plasminogen activator inhibitor-1 (PAI-1) (promoter 4G/5G) genes have been linked with coronary heart disease (CHD) a nd/or myocardial infarction (MI). We studied the association of polymorphis ms in these genes with CHD with linkage and association analyses in 118 fam ilies with premature and severe CHD and in 110 healthy controls. In linkage analysis there was no evidence for a linkage of the ACE or PAI-I loci with CHD. However, in quantitative linkage analysis the ACE locus was linked wi th fasting glucose (P = 0.047) and fasting free fatty acid levels (P = 0.02 9). In association analysis the ACE genotype frequencies of probands with C HD did not differ from those of healthy controls. Normoglycemic probands wi th MI and with the ACE polymorphism DD genotype had characteristics of the insulin resistance syndrome. They had higher levels of 1-h glucose (P = 0.0 08) and 2-h free fatty acids (P = 0.011) in an oral glucose tolerance test and higher levels of total (P = 0.005) and very-low-density lipoprotein tri glycerides (P = 0.006) than probands with the ID or the II genotypes. The P AI-1 gene polymorphism was not associated with any of the variables of gluc ose or lipid metabolism. In conclusion, the ACE and PAI-1 gene polymorphism s are not linked with early-onset CHD. However, the ACE gene polymorphism i s associated with features of the insulin resistance syndrome. (C) 2001 Els evier Science Ireland Ltd. All rights reserved.