The relationship of APOE polymorphism and cholesterol levels in normoglycemic and diabetic subjects in a biethnic population from the San Luis Valley, Colorado

Abstract

We have determined apolipoprotein E (apoE = protein, APOE = gene) polymorphism and its relationship with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels in normoglycemic Hispanics ( n = 446) and non-Hispanic whites (NHWs) ( n = 659) as well as in diabetic Hispanics ( n = 235) and NHWs ( n= 116) from the San Luis Valley, Colorado. Effects were estimated separately for each group, and within each group men and women were analyzed separately; women were further categorized into pre- and post-menopausal status. The distribution of the APOE genotype pattern was comparable between the NHW normoglycemics and diabetics but it was significantly different among Hispanic normoglycemics and diabetics ( P < 0.005). In the normoglycemic sample the APOE allele frequencies were significantly different between the two ethnic groups: the APOE ∗2(0.09 vs. 0.05; P < 0.01) and APOE∗4 (0.15 vs. 0.09; P < 0.002) allele frequencies were higher while the APOE ∗3 (0.76 vs. 0.86; P < 0.0001) allele frequency was lower in NHWs than in Hispanics. Significant variability among the three common APOE genotypes (3-2, 3-3, and 4-3) was observed for TC and LDL-C in normoglycemic Hispanic women ( P = 0.09 and P = 0.03) but not in Hispanic men. In normoglycemic NHWs, however, significant mean differences among APOE genotypes were observed for TC and LDL-C in both women ( P < 0.0001 and P < 0.0001) and men ( P = 0.009 and P = 0.01). In Hispanic females, the APOE polymorphism accounted for 5.6% and 7.6% of the phenotypic variance for TC and LDL-C, respectively. In NHW females, the APOE polymorphism explained 10.2% of the phenotypic variance for TC and LDL-C, and in NHW males these values were 6.2% and 7.5%, respectively. There was no evidence of physiologic interaction between the APOE polymorphism and menopause status in affecting TC and LDL-C in NHW women ( P = 0.65 and P = 0.55) but a suggestion of interaction was observed in Hispanic women for TC and LDL-C ( P = 0.11 and 0.07). After the Hispanic women were stratified into pre- and postmenopausal groups, the effect of the APOE polymorphism on TC and LDL-C was significant only in the premenopausal group. Among diabetics, no significant effect of the APOE polymorphism was seen on cholesterol levels. However, a significant relationship was observed between the APOE polymorphism and glycemic control in affecting cholesterol levels in Hispanics in which cholesterol varied significantly among APOE genotypes only in those diabetic individuals whose glycosylated hemoglobin was > 10.5%.