The associations of the polymorphism with atherosclerosis and myocardial infarction were studied in the Helsinki sudden death study, a prospective series of necropsies of white Finnish men who died suddenly.3
Atherosclerotic changes in the coronary arteries were measured by computer assisted planimetry, and coronary narrowings were determined from plastic casts.3
The presence of myocardial infarction was confirmed by macroscopic and histological examination of the myocardium. We selected the 119 cases (with mean age 53.4 (SD 8) years) for our analyses according to phenotype—52 men with severe coronary atherosclerosis (mean coronary stenosis 65.9% (10.8%)) and 67 men with only slightly narrowed coronary arteries (mean 22.1% (13.7%)). The causes of deaths were coronary heart disease in 59, violent death or accident in 38, and other diseases in 22. DNA was extracted from blood by a standard method, amplified by polymerase chain reaction, and analysed by capillary gel electrophoresis as described previously.4
Because of the large number of dinucleotide repeats,4
we used the median number of the repeat (n=19) to categorise the study population into three groups: those with short allele genotypes (both alleles of <19 repeats), those with long allele genotypes (both alleles of
19 repeats), and those with mixed genotypes (one short and one long allele). In analysis of covariance, with age and body mass index as covariates, men with long allele genotypes had a significantly greater number of severely narrowed coronary arteries (P=0.009), larger areas of complicated lesions (P=0.008), and more calcification of the coronary arteries (P=0.01) than men with short alleles (see figure). Atherosclerotic changes in the mixed genotype group were intermediate and not significantly different from those in the short or long allele genotype group.
A stepwise logistic regression analysis with age and body mass index as covariates showed that the group with long allele genotypes had a higher risk of myocardial infarction compared with the group with short allele genotypes (odds ratio 4.4 (95% confidence interval 1.21 to 15.70); P=0.025) and seemed to be more predisposed to coronary thrombosis (odds ratio 11.4 (1.2 to 108.8); P=0.04). When all confounding factors (age, body mass index, smoking, alcohol consumption, diabetes, hypertension) were forced in statistical models, the tendencies of the results were the same, but the small number of cases with all data (n=42) weakened the statistical significance.