Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels

Familial combined hyperlipidemia (FCHL) is a common dyslipidemia predisposi ng to premature coronary heart disease (CHD). The disease is characterized by increased levels of serum total cholesterol (TC), triglycerides (TGs), o r both. We recently localized the first locus for FCHL, on chromosome 1q21- q23. In the present study, a genomewide screen for additional FCHL loci was performed. In stage 1, we genotyped 368 polymorphic markers in 35 carefull y characterized Finnish FCHL families. We identified six chromosomal region s with markers showing LOD score (Z) values >1.0, by using a dominant mode of inheritance for the FCHL trait. In addition, two more regions emerged sh owing Z > 2.0 with a TG trait. In stage 2, we genotyped 26 more markers and seven additional FCHL families for these interesting regions. Two chromoso mal regions revealed Z > 2.0 in the linkage analysis: 10p11.2, Z = 3.20 (th eta = .00), with the TG trait; and 21q21, Z = 2.24 (theta = .10), with the apoB trait. Furthermore, two more chromosomal regions produced Z > 2.0 in t he affected-sib-pair analysis: 10q11.2-10qter produced Z = 2.59 with the TC trait and Z = 2.29 with FCHL, and 2q31 produced Z = 2.25 with the TG trait . Our results suggest additional putative loci influencing FCHL in Finnish families, some potentially affecting TG levels and some potentially affecti ng TC or apoB levels.