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PMID: 10417282 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11.

American journal of human genetics ·Vol. 65 ·No. 2 ·1999-08-00 ·Pages 397-412

Aouizerat BE, Allayee H, Cantor RM, Davis RC, Lanning CD, Wen PZ, Dallinga-Thie GM, de Bruin TW, Rotter JI, Lusis AJ

Abstract

Familial combined hyperlipidemia (FCHL) is a common familial lipid disorder characterized by a variable pattern of elevated levels of plasma cholesterol and/or triglycerides. It is present in 10%-20% of patients with premature coronary heart disease. The genetic etiology of the disease, including the number of genes involved and the magnitude of their effects, is unknown. Using a subset of 35 Dutch families ascertained for FCHL, we screened the genome, with a panel of 399 genetic markers, for chromosomal regions linked to genes contributing to FCHL. The results were analyzed by use of parametric-linkage methods in a two-stage study design. Four loci, on chromosomes 2p, 11p, 16q, and 19q, exhibited suggestive evidence for linkage with FCHL (LOD scores of 1.3-2.6). Markers within each of these regions were then examined in the original sample and in additional Dutch families with FCHL. The locus on chromosome 2 failed to show evidence for linkage, and the loci on chromosome 16q and 19q yielded only equivocal or suggestive evidence for linkage. However, one locus, near marker D11S1324 on the short arm of human chromosome 11, continued to show evidence for linkage with FCHL, in the second stage of this design. This region does not contain any strong candidate genes. These results provide evidence for a candidate chromosomal region for FCHL and support the concept that FCHL is complex and heterogeneous.

MeSH Terms
Adult Chromosomes, Human, Pair 11/genetics Female Genetic Linkage Genetic Markers Genome, Human Genotype Humans Hyperlipidemia, Familial Combined/genetics Male Matched-Pair Analysis Middle Aged Molecular Sequence Data Multifactorial Inheritance Netherlands Nuclear Family Pedigree Research Design Statistics, Nonparametric
Chemicals
Genetic Markers
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Aouizerat B E
Departments of 1Microbiology and Molecular Genetics, Medicine, Human Genetics, Molecular Biology Institute, University of California, UCLA School of Medicine Los Angeles, CA 90095-1679, USA.
Allayee H
Cantor R M
Davis R C
Lanning C D
Wen P Z
Dallinga-Thie G M
de Bruin T W
Rotter J I
Lusis A J
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302490
Published
1999-08-00
Pages
397-412
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1377938
Subset
IM
Grants
NHLBI NIH HHS · HL-28481 · United States
NCRR NIH HHS · P41 RR03655 · United States
Databases
OMIM
144250
External Links
PubMed source DOI: 10.1086/302490 PMC Full Text View journal details
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