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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2070.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Confirmed Locus on Chromosome 11p and Candidate Loci on 6q and 8p for the Triglyceride and Cholesterol Traits of Combined Hyperlipidemia

Rossitza P. Naoumova; Stephanie A. Bonney; Sophie Eichenbaum-Voline; Hetal N. Patel; Bethan Jones; Emma L. Jones; Joanna Amey; Susan Colilla; Clare K.Y. Neuwirth; Rebecca Allotey; Mary Seed; D. John Betteridge; David J. Galton; Nancy J. Cox; Graeme I. Bell; James Scott; Carol C. Shoulders

From the Genomic and Molecular Medicine Group (R.P.N., S.A.B., S.E.-V., H.N.P., B.J., E.L.J., J.A., C.K.Y.N., C.C.S.), Medical Research Council Clinical Sciences Centre, Hammersmith Hospital; Department of Cardiovascular Medicine (M.S.), Charing Cross Hospital; and Genetics and Genomics Research Institute (J.S.), Imperial College London, UK; Departments of Medicine and Human Genetics (S.C., N.J.C., G.I.B.) and Biochemistry and Molecular Biology (G.I.B.), Howard Hughes Medical Institute, University of Chicago, Ill; Department of Medicine (D.J.B.), Royal Free and University College Medical School, University College London, UK; and Departments of Diabetes and Metabolic Medicine (R.A.) and Human Metabolism and Genetics (D.J.G.), St Bartholomew’s Hospital, London, UK.

Correspondence to Dr Carol C. Shoulders or Professor James Scott, Genomic and Molecular Medicine Group, MRC Clinical Sciences Centre, Imperial College London, DuCane Rd, London W12 0NN, UK. E-mail carol.shoulders{at}csc.mrc.ac.uk or j.scott{at}imperial.ac.uk

Background— Combined hyperlipidemia is a common disorder characterized by a highly atherogenic lipoprotein profile and increased risk of coronary heart disease. The etiology of the lipid abnormalities (increased serum cholesterol and triglyceride or either lipid alone) is unknown.

Methods and Results— We assembled 2 large cohorts of families with familial combined hyperlipidemia (FCHL) and performed disease and quantitative trait linkage analyses to evaluate the inheritance of the lipid abnormalities. Chromosomal regions 6q16.1-q16.3, 8p23.3-p22, and 11p14.1-q12.1 produced evidence for linkage to FCHL. Chromosomes 6 and 8 are newly identified candidate loci that may respectively contribute to the triglyceride (logarithm of odds [LOD], 1.43; P=0.005) and cholesterol (LOD, 2.2; P=0.0007) components of this condition. The data for chromosome 11 readily fulfil the guidelines required for a confirmed linkage. The causative alleles may contribute to the inheritance of the cholesterol (LOD, 2.04 at 35.2 cM; P=0.0011) component of FCHL as well as the triglyceride trait (LOD, 2.7 at 48.7 cM; P=0.0002).

Conclusions— Genetic analyses identify 2 potentially new loci for FCHL and provide important positional information for cloning the genes within the chromosome 11p14.1-q12.1 interval that contributes to the lipid abnormalities of this highly atherogenic disorder.

Key Words: combined hyperlipidemia • lipid abnormalities • complex genetic disorder • chromosome 11p14.1-q12.1 • metabolic syndrome

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