Wojciechowski A P, Farrall M, Cullen P, Wilson T M, Bayliss J D, Farren B, Griffin B A, Caslake M J, Packard C J, Shepherd J
Division of Molecular Medicine, MRC Clinical Research Centre, Northwich Park Hospital, Harrow, Middlesex, UK.
Nature. 1991 Jan 10;349(6305):161-4. doi: 10.1038/349161a0.
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. 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. 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, zeta = 6.86 with no recombinants. This assignment will facilitate the identification of the mutation that causes hyperlipidaemia in these families.
