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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1998;18:1810-1817.)
© 1998 American Heart Association, Inc.

Original Contributions

Haplotypes of the ApoA-I/C-III/A-IV Gene Cluster and Familial Combined Hyperlipidemia

Esa Tahvanainen; Päivi Pajukanta; Kimmo Porkka; Sari Nieminen; Liisa Ikävalko; Ilpo Nuotio; Marja-Riitta Taskinen; Leena Peltonen; ; Christian Ehnholm

From the Department of Biochemistry, National Public Health Institute, Helsinki (E.T., S.N., L.I., C.E.); the Department of Human Molecular Genetics, National Public Health Institute, Helsinki (P.P., L.P.); the Department of Medicine, Helsinki University Central Hospital, Helsinki (K.P., M.-R.T.); and the Department of Medicine, University of Turku, Turku (I.N.), Finland.

Correspondence to Christian Ehnholm, Department of Biochemistry, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland. E-mail Christian.Ehnholm{at}ktl.fi

Abstract—Familial combined hyperlipidemia (FCHL) is the most frequent familial lipoprotein disorder associated with premature coronary heart disease. However, no genetic defect(s) underlying FCHL has been identified. A linkage between FCHL and the apoA-I/C-III/A-IV gene cluster has been reported but not verified in other populations. A recent study identified FCHL susceptibility haplotypes at this gene cluster. To study whether such haplotypes are also associated with FCHL susceptibility in Finns, we studied 600 well-defined Finnish FCHL patients and their relatives belonging to 28 extended FCHL families by using haplotype, linkage, sib-pair, and linkage disequilibrium analyses. The genotypes of the MspI polymorphisms were associated with total serum cholesterol (P<0.01) and apoB (P<0.05) levels in spouses, which represent the general Finnish population. However, no evidence of direct involvement of any of these loci or their specific haplotypes in the expression of FCHL in the Finnish FCHL families was found.

Key Words: apoA-I • apoC-III • apoA-IV • familial combined hyperlipidemia • coronary heart disease

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