FAMILIAL COMBINED HYPERLIPEMIA LINKED TO THE APOLIPOPROTEIN AI-CIII-AIV GENE-CLUSTER ON CHROMOSOME-11Q23-Q24

Familial combined hyperlipidaemia (FCHL) is a common inherited disorder of lipid metabolism with a prevalence of 0.5-2.0% (refs 1,2). It is estimated to cause 10% of premature coronary heart disease 1,3. The underlying metabolic and genetic defects in FCHL have not been identified, but a population study has suggested an association between FCHL and an XmnI restriction fragment length polymorphism (RFLP) within the apolipoprotein AI-CIII-AIV gene cluster 4. Here we confirm this association and show that it results from linkage disequilibrium between FChl and the 6.6-kilobase (kb) allele of the XmnI RFLP. Subsequent analysis in seven FChl families, ascertained through a proband carrying the 6.6 kb XmnI allele, demonstrated linkage to the AI-CIII-AIV cluster on 11q23-q24, z = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.