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CYP4A11 variant is associated with high-density lipoprotein cholesterol in women

The Pharmacogenomics Journal volume 13, pages 44–51 (2013)Cite this article

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Abstract

The ω-hydroxylase CYP4A11 catalyzes the transformation of epoxyeicosatrienoic acids (EETs) to ω-hydroxylated EETs, endogenous peroxisome proliferator-activated receptor-α (PPARα) agonists. PPARα activation increases high-density lipoprotein cholesterol (HDL-C). A cytosine-for-thymidine (T8590C) variant of CYP4A11 encodes for an ω-hydroxylase with reduced activity. This study examined the relationship between CYP4A11 T8590C genotype and metabolic parameters in the Framingham Offspring Study and in a clinical practice-based biobank, BioVU. In women in the Framingham Offspring Study, the CYP4A11 8590C allele was associated with reduced HDL-C concentrations (52.1±0.5 mg dl−1 in CYP4A11 CC- or CT-genotype women versus 54.8±0.5 mg dl−1 in TT women at visit 2, P=0.02), and with an increased prevalence of low HDL-C, defined categorically as ⩽50 mg dl−1 (odds ratio 1.39 (95% CI 1.02–1.90), P=0.04). In the BioVU cohort, the CYP4A11 8590C allele was also associated with low HDL-C in women (odds ratio 1.69 (95% CI 1.03–2.77, P=0.04)). There was no relationship between genotype and HDL-C in men in either cohort.

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Acknowledgements

This work was funded by Vanderbilt CTSA grant 1 UL1 RR024975, and by NIH Grants R01 HL060906, R01 DK080007 and P01 DK038226. The Framingham Studies are also supported by a contract from the National Heart, Lung and Blood Institute (contract no. N01-HC-25195).

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Author notes

  1. C C White and Q Feng: These authors contributed equally to this work.

  2. R A Wilke and N J Brown: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    C C White & L A Cupples

  2. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA

    Q Feng, J V Gainer, R A Wilke & N J Brown

  3. Framingham Heart Study, Framingham, MA, USA

    L A Cupples

  4. BioVentures, Murfreesboro, TN, USA

    E P Dawson

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  1. C C White
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Correspondence to N J Brown.

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White, C., Feng, Q., Cupples, L. et al. CYP4A11 variant is associated with high-density lipoprotein cholesterol in women. Pharmacogenomics J 13, 44–51 (2013). https://doi.org/10.1038/tpj.2011.40

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