GENOTYPE AT A MAJOR LOCUS WITH LARGE EFFECTS ON APOLIPOPROTEIN-B LEVELS PREDICTS FAMILIAL COMBINED HYPERLIPIDEMIA

A sample enriched for familial combined hyperlipidemia (FCHL) was exam ined for evidence of an association between genotype at an apolipoprot ein B (apoB) elevating locus defined by complex segregation analysis a nd FCHL. Complex segregation analysis detected a locus with a large ef fect on plasma apoB levels and was used to compute the most probable g enotype of family members. None of the 35 normolipidemic adults carrie d a copy of the allele associated with elevated apoB levels, yet 58% o f the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 2 8 (7%) normal children had 1 copy of this allele and none had 2 copies , while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copi es. Further, 41 of 48 (85%) individuals classified as having hyperapob etalipoproteinemia did not carry a copy of this ''elevated apoB'' alle le. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot b e explained solely by the presence of elevated apoB levels in FCHL, su ggesting that the locus controlling apoB levels may play an etiologic role in FCHL. (C) 1993 Wiley-Liss. Inc.