Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes. The Strong Heart Study.

Apo E is an important genetic factor in the development of cardiovascular disease, which is the leading cause of death among American Indians. We investigated the occurrence of the apo E alleles and the relation between apo E polymorphism and blood lipoproteins and apoproteins in members of 13 American Indian communities in three geographic areas. The frequencies of the epsilon 2 alleles in American Indians are significantly lower than those in white Americans, with the lowest frequencies of epsilon 2 in American Indians who reside in Arizona. Levels of LDL cholesterol and apo B were highest in those with epsilon 4 and lowest in those with epsilon 2. Concentrations of HDL cholesterol and apo A-I, however, tended to be lowest in epsilon 4 and highest in epsilon 2. Concentrations of total and VLDL triglycerides were lowest in the epsilon 3 group and higher in groups epsilon 2 and epsilon 4. Differences in concentrations of LDL cholesterol, HDL cholesterol, apo B, and apo A-I with apo E polymorphism were greater in women than in men, and differences in total and VLDL triglyceride concentrations by apo E phenotype were greater in men. Relations of total and VLDL triglycerides with apo E phenotype were stronger in women after menopause. In addition, differences in nearly all lipid and apoprotein concentrations between postmenopausal women and premenopausal women were greater if they had epsilon 2. Relations between apo E phenotype and lipoproteins were seen in individuals with diabetes mellitus as well as in nondiabetics. Apo E was significantly related to glucose control in diabetic women; those with epsilon 3 had higher glucose and hemoglobin A1C concentrations. Our findings show that (1) American Indians have low frequencies of apo epsilon 2; (2) apo E phenotype can influence levels of VLDL, LDL, HDL, apo B, and apo A-I; (3) the associations of apo E polymorphisms with lipid parameters differ between men and women; and (4) the associations in women of apo E polymorphisms with lipid parameters are modified by menopausal status.