SIB-PAIR ANALYSIS DETECTS ELEVATED LP(A) LEVELS AND LARGE VARIATION OF LP(A) CONCENTRATION IN SUBJECTS WITH FAMILIAR DEFECTIVE APO-B

Whether or not Lp(a) plasma levels are affected by the apoB R3500Q mut ation, which causes Familial Defective apoB (FDB), is still a matter o f debate. We have analyzed 300 family members of 13 unrelated Dutch in dex patients for the apoB mutation and the apolipoprotein(a) [apo(a)] genotype. Total cholesterol, LDL-cholesterol, and lipoprotein(a) [Lp(a )] concentrations were determined in 85 FDB heterozygotes and 106 non- FDB relatives. Mean LDL levels were significantly elevated in FDB subj ects compared to non-FDB relatives (P <0.001). Median Lp(a) levels wer e not different between FDB subjects and their non-FDB relatives. In c ontrast, sib-pair analysis demonstrated a significant effect of the FD B status on Lp(a) levels. In sib pairs identical by descent for apo(a) alleles but discordant for the FDB mutation (n=11) each sib with FDB had a higher Lp(a) level than the corresponding non-FDB sib. Further, all possible sib pairs (n=105) were grouped into three categories acco rding to the absence/presence of the apoB R3500Q mutation in one or bo th subjects of a sib pair, The variability of differences in Lp(a) lev els within the sib pairs increased with the number (0, 1, and 2) of FD B subjects present in the sib pair. This suggests that the FDB status increases Lp(a) level and variability, and that apoB may be a variabil ity gene for Lp(a) levels in plasma.