CYP4A11 variant is associated with high density lipoprotein cholesterol in women

The ω-hydroxylase CYP4A11 catalyzes the transformation of epoxyeicosatrienoic acids to omega-hydroxylated-epoxyeicosatrienoic acids, 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 a 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 (54.2±0.9 mg/dL in CYP4A11 CC or CT genotype women versus 56.7±0.5 mg/dL in TT women, p=0.02), and with an increased prevalence of low HDL-C, defined categorically as ≤50mg/dL [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.