Sex Differences in Blood HDL-c, the Total Cholesterol/HDL-c Ratio, and Palmitoleic Acid are Not Associated with Variants in Common Candidate Genes

Abstract

Blood lipids are associated with cardiovascular disease (CVD) risk. Moreover, circulating lipid and fatty acid levels vary between men and women, and evidence demonstrates these traits may be influenced by single nucleotide polymorphisms (SNP). Sex-genotype interactions related to blood lipids and fatty acids have been poorly investigated and may help elucidate sex differences in CVD risk. The goal of this study was to investigate if the influence of SNPs previously associated with blood lipids and fatty acids varies in a sex-specific manner. Lipids and fatty acids were measured in serum and red blood cells (RBC), respectively, in 94 adults (18-30 years) from the GONE FISHIN' cohort and 118 age-matched individuals from the GOLDN cohort. HDL-c levels were higher and the total cholesterol/HDL-c (TC/HDL-c) ratio was lower in women versus men (p < 0.01). RBC palmitoleic acid and the stearoyl-CoA desaturase index were both higher in women (p < 0.01). Fatty acid desaturase (FADS) pathway activity (estimated using the ratio of eicosapentaenoic acid/alpha-linolenic acid) was higher in men (p < 0.01). The AA genotype for rs1800775 in CETP had a lower TC/HDL-c ratio in men, but not women (p int = 0.03). Independent of sex, major alleles for rs174537 in FADS1 (GG) and rs3211956 in CD36 (TT) had higher arachidonic acid, lower dihomo-γ-linoleic acid, and a higher FADS1 activity compared to minor alleles. The current study showed that blood lipid and fatty acid levels vary between healthy young men and women, but that the observed sex differences are not associated with common variants in candidate lipid metabolism genes.

Keywords: CD36; CETP; Cardiovascular risk; Fatty acid desaturase; Palmitoleic acid; SNP.

Figures

Fig. 1

Significant associations between FA and SNPs in FADS1 and CD36. Relative percentage for AA (20:4n-6) (a) and DGLA (20:3n-6) (b) in participants stratified as major (GG) or minor (GT+TT) carriers of rs174537 in FADS1. (c) FADS1 activity estimate (i.e., 20:4n-6/20:3n-6) in participants stratified as major (TT) or minor (GT+GG) for rs3211956 in CD36. Data is reported as mean% ± SEM. p values correspond to post hoc analyses following a two-way ANOVA