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Papers In Press, published online ahead of print January 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600184-JLR200

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Journal of Lipid Research, Vol. 48, 193-200, January 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Patient-Oriented Research

The involvement of upstream stimulatory factor 1 in Dutch patients with familial combined hyperlipidemia

Gerly M. van der Vleuten^*, Aaron Isaacs, Anneke Hijmans^*, Cornelia M. van Duijn, Anton F. H. Stalenhoef^* and Jacqueline de Graaf^1,*

^* Department of Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Department of Epidemiology and Biostatistics, Genetic Epidemiology Unit, Erasmus Medical Center, Rotterdam, The Netherlands

The online version of this article (available at http://www.jlr.org) contains two additional tables.

Published, JLR Papers in Press, October 25, 2006.

¹ To whom correspondence should be addressed. e-mail: j.degraaf{at}aig.umcn.nl

ABSTRACT

Recently, the upstream stimulatory factor 1 gene (USF1) was proposed as a candidate gene for familial combined hyperlipidemia (FCH). In this study, we examined the previously identified risk haplotype of USF1 with respect to FCH and its related phenotypes in 36 Dutch FCH families. The diagnosis of FCH was based on both the traditional diagnostic criteria and a nomogram. The two polymorphisms, USF1s1 and USF1s2, were in complete linkage disequilibrium. No association was found for the individual single nucleotide polymorphisms (SNPs) with FCH defined by the nomogram (USF1s1, P = 0.53; USF1s2, P = 0.53), whereas suggestive associations were found when using the traditional diagnostic criteria for FCH (USF1s1, P = 0.08; USF1s2, P = 0.07). USF1 was associated with total cholesterol (USF1s1, P = 0.05; USF1s2, P = 0.04) and apolipoprotein B (USF1s1, P = 0.06; USF1s2, P = 0.04). Small dense LDL showed a suggestive association (USF1s1, P = 0.10; USF1s2, P = 0.09). The results from the haplotype analyses supported the results obtained for the individual SNPs. In conclusion, the previously identified risk haplotype of USF1 showed a suggestive association with FCH and contributed to the related lipid traits in our Dutch FCH families.

Supplementary key words single nucleotide polymorphisms • mRNA expression • total cholesterol • apolipoprotein B • small dense low density lipoprotein

Abbreviations: apoB, apolipoprotein B; CHD, coronary heart disease; CVD, cardiovascular disease; FBAT, family-based association test; FCH, familial combined hyperlipidemia; HBAT, haplotype-based association test; HOMA, homeostasis model assessment; HSL, hormone-sensitive lipase; LDL-c, low density lipoprotein cholesterol; lod, log of the odds; PBAT, pedigree-based association test; PBMC, peripheral blood mononuclear cell; sdLDL, small dense low density lipoprotein; SNP, single nucleotide polymorphism; TC, total cholesterol; TG, triglyceride; TXNIP, thioredoxin-interacting protein; USF1, upstream stimulatory factor 1

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