APOLIPOPROTEIN-E POLYMORPHISM IN AMERICAN-INDIANS AND ITS RELATION TOPLASMA-LIPOPROTEINS AND DIABETES - THE STRONG HEART-STUDY

Apo E is an important genetic factor in the development of cardiovascu lar disease, which is the leading cause of death among American Indian s. We investigated the occurrence of the apo E alleles and the relatio n 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 signi ficantly lower than those in white Americans, with the lowest frequenc ies 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 low est 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. Differen ces 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 ph enotype were greater in men. Relations of total and VLDL triglycerides with apo E phenotype were stronger in women after menopause. In addit ion, differences in nearly all lipid and apoprotein concentrations bet ween postmenopausal women and premenopausal women were greater if they had epsilon 2. Relations between apo E phenotype and lipoproteins wer e seen in individuals with diabetes mellitus as well as in nondiabetic s. Apo E was significantly related to glucose control in diabetic wome n; those with epsilon 3 had higher glucose and hemoglobin A(1c) concen trations. Our findings show that (1) American Indians have low frequen cies of apo epsilon 2; (2) apo E phenotype can influence levels of VLD L, LDL, HDL, apo B, and apo A-I; (3) the associations of apo E polymor phisms with lipid parameters differ between men and women; and (4) the associations in women of apo E polymorphisms with lipid parameters ar e modified by menopausal status.