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Title: Sex differences in blood HDL-c, the total cholesterol/HDL-c ratio, and palmitoleic acid are not associated with variants in common candidate genes

Author
item KLINGEL, SHANNON - University Of Guelph
item ROKE, KAITLIN - University Of Guelph
item HIDALGO, BERTHA - University Of Alabama
item ASLIBEKYAN, STELLA - University Of Alabama
item STRAKA, ROBERT - University Of Minnesota
item AN, PING - Washington University
item PROVINCE, MICHAEL - Washington University
item HOPKINS, PAUL - University Of Utah
item ARNETT, DONNA - University Of Kentucky
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Lai, Chao Qiang
item MUTCH, DAVID - University Of Guelph

Submitted to: Lipids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/2017
Publication Date: 10/27/2017
Citation: Klingel, S.L., Roke, K., Hidalgo, B., Aslibekyan, S., Straka, R.J., An, P., Province, M.A., Hopkins, P.N., Arnett, D.K., Ordovas, J.M., Lai, C., Mutch, D.M. 2017. Sex differences in blood HDL-c, the total cholesterol/HDL-c ratio, and palmitoleic acid are not associated with variants in common candidate genes. Lipids. 52(12):969-980. https://doi.org/10.1007/s11745-017-4307-5.
DOI: https://doi.org/10.1007/s11745-017-4307-5

Interpretive Summary: Blood lipids are biomarkers for cardiovascular disease (CVD) risk. Blood lipids differ between men and women, but little is known about the genetic basis of such differences. This study was to examine a set of 22 common genetic variants that are associated with blood lipids in general populations with differences in HDC-c and fatty acids in the blood between men and women. The findings indicate some variants are associated with blood lipids in two groups of men and women, but there is no association between these variants and the observed sex differences in HDL-c and blood fatty acids.

Technical 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 (SNPs). 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 (RBCs), respectively, in 94 adults (18-30 yrs) 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-y-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.