To study the genetic influence on serum cholesterol levels and early coronary heart disease, 1,134 individuals were screened from 18 Utah pedigrees. In most pedigrees, serum cholesterol appeared to be a purely polygenic trait, with 54% heritability. In four pedigrees with dominant familial hypercholesterolemia, male heterozygotes had a mean serum cholesterol level of 352 mb/dL, myocardial infarction at an average age of 42 years, and coronary death at an average age of 45 years. An informative pedigree structure allowed the identification of four ancestral males born before 1880 who carried this lethal gene and survived to ages 62, 68, 72, and 81 years. This suggests that some healthy life-style factors protected these men against the expression of a gene that has led to coronary disease by age 45 years in all of their heterozygous great-grandsons. One heterozygote showed a drop in serum cholesterol level from 426 to 248 mg/dL, with strict adherence to a low-fat diet without drugs. These observations should help encourage physicians to try harder to identify and help such individuals.
Williams RR, Hasstedt SJ, Wilson DE, Ash KO, Yanowitz FF, Reiber GE, Kuida H. Evidence That Men With Familial Hypercholesterolemia Can Avoid Early Coronary DeathAn Analysis of 77 Gene Carriers in Four Utah Pedigrees. JAMA. 1986;255(2):219–224. doi:10.1001/jama.1986.03370020065029