Familial combined hyperlipidaemia linked to the apolipoprotein AI–CIII–AIV gene cluster on chromosome 11q23q–q24

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Abstract
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 disease1,3. 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 cluster4. 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 kbXmnI allele, demonstrated linkage to the AI–CIII–AIV cluster on 1lq23–q24, ẑ= 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.