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Papers In Press, published online ahead of print August 1, 2008
J. Lipid Res., doi:10.1194/jlr.M700490-JLR200

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Journal of Lipid Research, Vol. 49, 1701-1706, August 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study^*,

Kathy L. E. Klos^1,*, Eric Boerwinkle^*, Robert E. Ferrell, Stephen T. Turner and Alanna C. Morrison^*

^* Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX
Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN

^* Support for this work was provided by National Heart, Lung, and Blood Institute Grant R01- HL-077491.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one table.

Published, JLR Papers in Press, April 30, 2008.

¹ To whom correspondence should be addressed. e-mail: kathy.klos{at}uth.tmc.edu

We evaluated six estrogen receptor 1 (ESR1) polymorphisms for association with ten plasma lipid and apolipoprotein traits in 1,847 individuals (941 females and 906 males) in the multi-generation Rochester Family Heart Study using a generalized estimating equation approach. Apolipoprotein A-I (apoA-I), apoA-II, and HDL-cholesterol (HDL-C) were associated with exon 4 rs1801132 (Pro325Pro) genotype (P = 0.0044, P = 0.0048, and P = 0.0035, respectively). Positive correlation between levels of apoA-I, apoA-II, and HDL-C and the number of G alleles was observed in females (P = 0.0120, P = 0.0032, and P = 0.0030), but not males (P > 0.05). Because few studies have evaluated the effect of ESR1 gene polymorphisms on lipid traits in children, we also stratified our sample at the age of 15 years. There was evidence of association between intron 1 single-nucleotide polymorphisms rs9322331 and rs9340799 and apoC-II, and triglycerides (TGs) in youths 15 years and younger. In youths, evidence of association between rs9322331 and rs9340799 and apoC-II was stronger in males (P = 0.0036 and P = 0.0124) than in females (P > 0.05), whereas evidence of association with TG was stronger in females (P = 0.0030 and P = 0.0024) than in males (P > 0.05). These findings suggest that ESR1 variation plays an age- and sex-dependent role in determining plasma lipid and apolipoprotein levels.

Supplementary key words estrogen receptor 1 • HDL • LDL • triglycerides

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