Polymorphism in 5' flanking region of human insulin gene. Relationships with atherosclerosis, lipid levels, and age in three samples from Denmark.

Variations in the DNA sequence flanking the 5' region of the human insulin gene (U- and L-alleles) were studied in relation to atherosclerosis, lipid levels, and age in three groups of atherosclerotic individuals and in nonatherosclerotic controls. The atherosclerotic groups comprised a postmyocardial infarction group with a mean age of 48 years, a group of individuals operated on for carotid stenosis with a mean age of 62 years, and a group of 85-year-olds with clinical coronary disease, peripheral arterial disease, or both. All 331 individuals were unrelated Caucasians of Danish ancestry. There were no significant differences (p greater than 0.05) in genotype distribution or allele frequencies between atherosclerotic and nonatherosclerotic individuals, but in the 85-year-olds, there was evidence (p less than 0.10) for a lower U-allele frequency in nonatherosclerotic women compared to atherosclerotic women. In nonatherosclerotic women, there was a significant decrease in U-allele frequency with age (60 to 85 years). This decrease does not prove conclusively, but is compatible with, the hypothesis that the U-allele predisposes to, or the L-allele protects against, atherosclerosis. The possible effect of the U-allele on the development of atherosclerosis does not seem to be mediated through conventional risk factors.