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Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides

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Abstract

Positive evidence has been reported for linkage and association between the upstream stimulatory factor 1 gene (USF1) and familial combined hyperlipidemia (FCHL). We genotyped the two most positive single-nucleotide polymorphisms (SNPs) (usf1s1: rs3737787 and usf1s2: rs2073658) from previous studies in a large family sample. This sample included 2,195 subjects in 87 Utah pedigrees ascertained for early death due to coronary heart disease (CHD), early strokes, or early onset hypertension. There were a total of 262 relative pairs in these families with FCHL. In the full family sample, FCHL was associated with usf1s1 (P=0.02). Triglyceride and LDL cholesterol defined qualitatively or quantitatively were also associated with usf1s1 (P=0.02–0.05). Results were strengthened for qualitative and quantitative triglyceride and LDL cholesterol when data from males only was analyzed, revealing associations for usf1s1 (P=0.001–0.02), usf1s2 (P=0.02–0.05) and the haplotype of these two SNPs (P=0.01–0.04). The strongest results were in the subset of subjects from families ascertained for premature stroke or hypertension, rather than those ascertained for premature CHD. This study replicates the involvement of USF1 in FCHL and related lipid traits in a family sample not ascertained for FCHL.

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Acknowledgements

This research was supported by NIH grants HL21088, HL24855, HL44738, AG18734, and HD17463. We thank the subjects participating in this study.

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Authors and Affiliations

  1. Neurodevelopmental Genetics Project, Department of Psychiatry, University of Utah, Salt Lake City, UT, 84108, USA

    Hilary Coon

  2. Cardiovascular Genetics, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84108, USA

    Yuanpei Xin, Paul N. Hopkins & Steven C. Hunt

  3. Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA

    Richard M. Cawthon & Sandra J. Hasstedt

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  1. Hilary Coon
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  2. Yuanpei Xin
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  3. Paul N. Hopkins
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  4. Richard M. Cawthon
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  5. Sandra J. Hasstedt
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  6. Steven C. Hunt
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Correspondence to Hilary Coon.

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Coon, H., Xin, Y., Hopkins, P.N. et al. Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides. Hum Genet 117, 444–451 (2005). https://doi.org/10.1007/s00439-005-1340-x

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  • DOI: https://doi.org/10.1007/s00439-005-1340-x

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