J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M400141-JLR200 on July 16, 2004

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Journal of Lipid Research, Vol. 45, 1876-1884, October 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with dyslipidemia

Heidi E. Lilja*, Elina Suviolahti*, Aino Soro-Paavonen{dagger}, Tero Hiekkalinna*, Aaron Day§, Kenneth Lange§, Eric Sobel§, Marja-Riitta Taskinen{dagger}, Leena Peltonen1,*,§,**, Markus Perola* and Päivi Pajukanta1,§

* Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
{dagger} Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
§ Department of Human Genetics, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA
** Department of Medical Genetics, University of Helsinki, Helsinki, Finland

1 To whom correspondence should be addressed. e-mail: leena.peltonen{at}ktl.fi (L.P.); ppajukanta{at}mednet.ucla.edu (P.P.)

Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our previous pooled data analysis of the genome scans for low HDL-C and FCHL, which identified three shared chromosomal regions for a qualitative HDL-C trait on 8q23.1, 16q23.3, and 20q13.32. This study further investigates these regions as well as two other loci we identified earlier for premature CHD on 2q31 and Xq24 and a locus for high serum triglycerides (TGs) on 10q11. We analyzed 67 microsatellite markers in an extended study sample of 1,109 individuals from 92 low HDL-C or FCHL families using both qualitative and quantitative lipid phenotypes.

These analyses provided evidence for linkage (a logarithm of odds score of 3.2) on 10q11 using a quantitative HDL-C trait. Importantly, this region, previously linked to TGs, body mass index, and obesity, provided evidence for association for quantitative TGs (P = 0.0006) and for a combined trait of HDL-C and TGs (P = 0.008) with marker D10S546. Suggestive evidence for linkage also emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL-C and TGs.

Abbreviations: apoA-I, apolipoprotein A-I; BMI, body mass index; CHD, coronary heart disease; cM, centimorgan; FCHL, familial combined hyperlipidemia; HDL-C, high density lipoprotein-cholesterol; HDL2 and HDL3, high density lipoprotein cholesterol particles 2 and 3; LDLps, low density lipoprotein cholesterol particle size; QTL quantitative trait locus; TC, total cholesterol; TG, triglyceride

Supplementary key words low high density lipoprotein-cholesterol • familial combined hyperlipidemia • coronary heart disease • atherosclerosis • quantitative traits • variance component analyses • quantitative trait locus • triglycerides • type 2 diabetes • metabolic syndrome


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