Apolipoprotein A-IV Genetic Polymorphism and Its Impact on Quantitative Traits in Normoglycemic and Non-Insulin-Dependent Diabetic Hispanics from the San Luis Valley, Colorado

Apolipoprotein A -IV exhibits a common two-allele polymorphism in several human populations studied to date. Using isoelectric focusing and immunoblotting, we have analyzed plasmas from 188 non-insulin-dependent diabetic and 238 normoglycemic Hispanic individuals from the San Luis Valley, Colorado , to determine APOA 4 genotype frequencies and to estimate the impact of the genotypes on quantitative traits. The frequencies of the two common alleles, APOA 4 * l and AP OA 4 * 2 , were 0.929 and 0.069, respectively, in normal subjects and 0.901 and 0.096 , respectively, in diabetics. The third rare allele, APOA 4 * 3, was detected sporadically in both groups. We studied the impact of APOA 4 polymorphism on the levels of total plasma cholesterol, HDL cholesterol and its subfractions (HDL 3 and HDL 2), LDL cholesterol, triglycerides, glucose, and insulin. We observed no significant effect of the APOA4 polymorphism on any trait in diabetics. However, we did note a significant sex -specific effect in normoglycemic females on the level of total HDL cholesterol (p = 0.001 ) and its subfractions HDL2 (p = 0.043) and HDL3 (p = 0.001). The effect of the APOA 4 * 2 allele in normal Hispanic females was to low er the total HDL, HDL 2, and HDL 3 cholesterol by 8.75 mg /dl, 2.37 mg/dl, and 5.36 mg/dl, respectively , compared to the common APOA 4 * l allele