Confirmed locus on chromosome 11p and candidate loci on 6q and 8p for the triglyceride and cholesterol traits of combined hyperlipidemia

Background - Combined hyperlipidemia is a common disorder characterized by a highly atherogenic lipoprotein profile and increased risk of coronary heart disease. The etiology of the lipid abnormalities ( increased serum cholesterol and triglyceride or either lipid alone) is unknown. Methods and Results - We assembled 2 large cohorts of families with familial combined hyperlipidemia ( FCHL) and performed disease and quantitative trait linkage analyses to evaluate the inheritance of the lipid abnormalities. Chromosomal regions 6q16.1- q16.3, 8p23.3- p22, and 11p14.1- q12.1 produced evidence for linkage to FCHL. Chromosomes 6 and 8 are newly identified candidate loci that may respectively contribute to the triglyceride ( logarithm of odds [ LOD], 1.43; P = 0.005) and cholesterol ( LOD, 2.2; P = 0.0007) components of this condition. The data for chromosome 11 readily fulfil the guidelines required for a confirmed linkage. The causative alleles may contribute to the inheritance of the cholesterol ( LOD, 2.04 at 35.2 cM; P = 0.0011) component of FCHL as well as the triglyceride trait ( LOD, 2.7 at 48.7 cM; P = 0.0002). Conclusions - Genetic analyses identify 2 potentially new loci for FCHL and provide important positional information for cloning the genes within the chromosome 11p14.1- q12.1 interval that contributes to the lipid abnormalities of this highly atherogenic disorder.