Decrease with age in frequency of the homozygous deletional angiotensin-converting enzyme genotype in hypertensive patients.

1. Angiotensin-converting enzyme (ACE) genotypes in hypertensive patients were studied in order to delineate their cardiovascular risk due to the ACE gene. We hypothesized that the distribution of ACE genotypes may change with age because of the risk of myocardial infarction associated with the homozygous deletional (DD) genotype. 2. A total of 223 subjects were recruited from the Hypertension Outpatient Clinic of the Sai Ying Pun Hospital with consent. They consisted of 75 patients with newly diagnosed or documented hypertension, 46 patients with ischaemic heart disease and 102 normal controls. Genomic DNA was extracted from peripheral leucocytes and amplified by polymerase chain reaction. Insertion (I) or deletion (D) alleles were identified after electrophoresis. The frequencies of ACE genotypes and alleles were measured in three age groups: < 50 years, 50-59 years and > or = 60 years. 3. A significant correlation between ACE genotype and age was found (P = 0.03). The relative frequency of the D allele in those under 50 years of age was similar in controls and hypertensive patients (0.40 vs 0.41; P = 0.94), but was significantly lower in patients > or = 50 years compared with those patients < 50 years of age (0.22 vs 0.41; P = 0.01). 4. The observed decrease in frequency of the DD genotype in older hypertensive patients is consistent with the increase in cardiovascular risk associated with the D allele and raises the possibility that the DD genotype may increase the risk of premature death, at least in the population studied.