MAJOR LOCUS INFLUENCING PLASMA APO-A1 LEVELS ALSO CONTROLS PLASMA HDL3-C CONCENTRATIONS

Elevated plasma levels of apolipoprotein Al (APO-A1) and high-density lipoprotein cholesterol (HDL-C) are important protective factors for a therosclerosis and coronary heart disease. Using the data on plasma co ncentrations of APO-A1, and HDL-C particles HDL2-C and HDL3-C in 970 I sraeli individuals belonging to 228 pedigrees, we tested the hypothesi s that a major locus influencing interindividual variation in APO-A1 l evels also controls interindividual variation in HDL3-C and HDL2-C lev els. Univariate and bivariate complex segregation analyses, as impleme nted in two statistical packages (MAN-3 and PAP-4.0) were applied to t est the hypothesis. The results of the analysis clearly indicated the possibility of major gene involvement in the determination of plasma c oncentration variation of each of the 3 study variables. The results p rovide strong evidence in support of our hypothesis that HDL3-C geneti c variation fully depends on the APO-AI major locus. In particular; en vironmental and sporadic models were strongly rejected (P < 0.001) in bivariate analysis. The hypothesis of no pleiotropic effect of the put ative APO-A1 locus on HDL3-C transmission was also unequivocally rejec ted (P < 0.001), while the bivariate Mendelian model was accepted (P > 0.05). The results of bivariate analysis of APO-A1 effect on HDL2-C w ere not clear. They indicated the possibility of the existence of slig ht genetic covariation between the two variables, and as yet we were u nable to decipher the mode of covariation with the applied models. (C) 1998 Wiley-Liss, Inc.