Abstract
Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT). A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1) gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G) frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029). Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032). No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.
Highlights
Estrogen exerts beneficial systemic effects on lipoprotein and antioxidant metabolism through estrogen receptoralpha (ESR1) [1]
Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter these levels by decreasing low-density lipoprotein (LDL) cholesterol levels and increasing high-density lipoprotein (HDL) cholesterol levels [3,4]
The objective of the present study was to determine if there is an association between MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G ESR1 single nucleotide polymorphisms (SNP) and plasma HDL cholesterol levels in postmenopausal women who were treated with conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year
Summary
Estrogen exerts beneficial systemic effects on lipoprotein and antioxidant metabolism through estrogen receptoralpha (ESR1) [1]. It is clear that estrogen levels decline in women during menopause and that this is one reason for the increase in plasma low-density lipoprotein (LDL) levels. Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter these levels by decreasing LDL cholesterol levels and increasing HDL cholesterol levels [3,4]. HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT) and a significant portion of the variability in HDL cholesterol levels can be attributed to genetic factors [5,6,7]. The human ESR1 gene is located on the long arm of chromosome 6 (6q25.1) and contains 8 exons separated by 7 intronic regions [9,10]. Several single nucleotide polymorphisms (SNP) of the ESR1 gene have been identified, of which the MspI C>T (National Center for Biotechnology Information SNP identification, NCBI SNP ID: rs1784705) SNP in the first exon and HaeIII
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