title: CYP4A11 variant is associated with high-density lipoprotein cholesterol in women.
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.
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: C C
authors.initials: CC
authors.lastname: White
authors.forename: Q
authors.initials: Q
authors.lastname: Feng
authors.forename: L A
authors.initials: LA
authors.lastname: Cupples
authors.forename: J V
authors.initials: JV
authors.lastname: Gainer
authors.forename: E P
authors.initials: EP
authors.lastname: Dawson
authors.forename: R A
authors.initials: RA
authors.lastname: Wilke
authors.forename: N J
authors.initials: NJ
authors.lastname: Brown
mesh_terms: D000328:Adult; D000483:Alleles; D008076:Cholesterol, HDL / Q000235:genetics* / Q000378:metabolism*; D015331:Cohort Studies; D042926:Cytochrome P-450 CYP4A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male
chemical_list: D008076:Cholesterol, HDL; D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A