SIGNIFICANCE OF ANGIOTENSIN I-CONVERTING ENZYME AND ANGIOTENSIN-II TYPE-1 RECEPTOR GENE POLYMORPHISMS AS RISK-FACTORS FOR CORONARY HEART-DISEASE

The D allele of an insertion/deletion (I/D) polymorphism in the angiot ensin I-converting enzyme (ACE) gene is associated with a risk of myoc ardial infarction: and the relative risk associated with the ACE D all ele is increased by the C allele of an angiotensin II type 1 receptor (AT(1)R) gene polymorphism (an A --> C transversion al nucleotide posi tion 1166) [28]. The relation of the ACE and AT(1)R gene polymorphisms to coronary heart disease and the severity of coronary artery stenosi s has now been investigated in 133 patients with myocardial infarction (MI) or angina pectoris who underwent coronary angiography and in 258 control subjects. The frequency of the ACE DD genotype as compared wi th non-DD was significantly higher in the patients who experienced an MI and in the low-risk patients than that in the controls (P < 0.05). The DD genotype showed a significantly increased risk of MI (odds rati o 1.85). The frequency of the AT(1)R A/C genotypes did not differ betw een the patients and the controls. The severity of coronary stenosis i n the patients was estimated by the number of affected vessels (> 75% stenosis) and the coronary score of Gensini. Neither the number of aff ected vessels nor the coronary score differed among the ACE I/D genoty pes. However, the number of affected vessels was significantly greater in patients with the AT(1)R AC genotype than in those with the AA gen otype (1.93 +/- 0.27 vs. 1.27 +/- 0.99; P < 0.05) (CC genotype was not found in the patients). After excluding patients with diabetes mellit us, the coronary score of those with the AC genotype was also signific antly higher than in those with the AA genotype (51.7 +/- 34.4 vs. 18. 2 +/- 23.3; P < 0.01). These results suggest that the ACE D allele is associated with the occurrence of myocardial infarction, while the AT( 1)R C allele is involved in the development of the coronary artery ste nosis.