Evidence that men with familial hypercholesterolemia can avoid early coronary death. An analysis of 77 gene carriers in four Utah pedigrees
Williams, R.R.; Hasstedt, S.J.; Wilson, D.E.; Ash, K.O.; Yanowitz, F.F.; Reiber, G.E.; Kuida, H.
JAMA 255(2): 219-224
1986
ISSN/ISBN: 0098-7484 PMID: 3941501 Document Number: 280601
To study genetic influence on serum cholesterol and early coronary heart disease, 1134 persons were screened from 18 Utah, USA, pedigrees. In most pedigrees, serum cholesterol seemed to be a purely polygenic trait, with 54% heritability. In 4 pedigrees with dominant familial hypercholesterolaemia, male heterozygotes had mean serum cholesterol values of 352 mg/100 ml, myocardial infarction at on average 42 years and coronary death at on average 45 years. An informative pedigree structure allowed the identification of 4 ancestral men born before 1880 who carried that lethal gene and survived to 62, 68, 72 and 81 years old. That suggests that some healthy life-style factors protected those men against the expression of a gene which has led to coronary disease by 45 years old in all of their heterozygous great-grandsons. One heterozygote showed a decrease in serum cholesterol from 426 to 248 mg/100 ml, with strict adherence to a low-fat diet without drugs. The observations should encourage physicians to try harder to identify and help such persons.