Estrogen receptor-alpha variants are associated with lipoprotein size distribution and particle levels in women: the Framingham Heart Study.
Plasma lipid profile is affected by endogenous estrogen levels and hormone replacement therapy (HRT). As plasma lipid concentrations have a significant heritable basis and the effects of both endogenous estrogen and use of HRT are mediated by estrogen receptors, we sought to investigate the relationships between polymorphisms in estrogen receptor-alpha (ESR1) and plasma lipid and lipoprotein concentrations. We analyzed data from 854 women (mean age 52+/-10 years) from the Framingham Heart Study. A TA repeat in the promoter region, c.30T>C in exon 1, c.454-397T>C, and c.454-351A>G in intron 1, all in linkage disequilibrium (LD), were significantly associated with low-density lipoprotein (LDL) particle size and concentration of small LDL particles. Women with the c.454-397C allele had larger LDL particle size (21.09+/-0.02 nm versus 21.01+/-0.03 nm, p=0.021) concurrent with lower small LDL particle concentration (0.47+/-0.02 mmol/L versus 0.58+/-0.03 mmol/L, p=0.008). Moreover, the TA[L]-c.30C-c.454-397C-c.454-351G haplotype (frequency, 32%) was associated with lower small LDL particle concentrations (-0.06+/-0.03 mmol/L change associated with each copy of this haplotype, p=0.011) when compared to the TA[S]-c.30T-c.454-397T-c.454-351A haplotype (frequency, 46%), where L and S are long and short TA repeats. Our results suggest that common ESR1 polymorphisms have a significant effect on lipoprotein metabolism in women.
Demissie
Serkalem
S
Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, TE425 Boston, MA 02118, USA. demissie@bu.edu
Cupples
L Adrienne
LA
Shearman
Amanda M
AM
Gruenthal
Kristen M
KM
Peter
Inga
I
Schmid
Christopher H
CH
Karas
Richard H
RH
Housman
David E
DE
Mendelsohn
Michael E
ME
Ordovas
Jose M
JM
D000483:Alleles; D004247:DNA / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D006239:Haplotypes; D006331:Heart Diseases / Q000097:blood / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008077:Lipoproteins, LDL / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D008593:Menopause / Q000097:blood; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D008077:Lipoproteins, LDL; D004247:DNA