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An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Endogenous estradiol and its association with estrogen receptor gene polymorphisms
MaryFran R Sowers1, Mary L Jannausch, Daniel S McConnell
1Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104, USA. mfsowers@umich.edu
The American Journal of Medicine
|September 5, 2006
Summary
Estrogen receptor gene variants (ESR1, ESR2) showed weak associations with estradiol levels in diverse women. Specific single nucleotide polymorphism (SNP) genotypes explained less than 4% of estradiol variation across racial/ethnic groups.
Area of Science:
- Genetics and Genomics
- Endocrinology
- Reproductive Biology
Background:
- Estrogen receptors, ESR1 and ESR2, play crucial roles in regulating estradiol (E2) activity.
- Genetic variations, specifically single nucleotide polymorphisms (SNPs), in these receptor genes may influence E2 concentrations.
- Understanding these associations is important for comprehending hormonal variations in women across different ethnicities.
Purpose of the Study:
- To investigate potential links between specific single nucleotide polymorphism (SNP) variants in estrogen receptor genes (ESR1 and ESR2) and circulating estradiol (E2) levels.
- To examine these associations in a multi-racial/ethnic cohort of women.
Main Methods:
- Analysis of 1,538 women from the Study of Women's Health Across the Nation (SWAN) across African American, Caucasian, Chinese, and Japanese ethnicities.
- Genotyping of 4 ESR1 SNPs (rs9340799, rs2234693, rs728524, rs3798577) and 3 ESR2 SNPs (rs1255998, rs1256030, rs1256065).
- Measurement of circulating estradiol (E2) concentrations in premenopausal and perimenopausal women during the early follicular phase.
Main Results:
- Mean E2 levels varied by race/ethnicity, with Chinese and Japanese women exhibiting lower concentrations than African American and Caucasian women.
- The ESR1 rs3798577 CC genotype was tentatively linked to lower E2 in African American women, explaining ~1% of variation.
- In Japanese women, the ESR2 rs1255998 GC genotype was associated with significantly lower E2, explaining ~4% of variation.
Conclusions:
- Circulating estradiol concentrations were not strongly or consistently associated with the selected estrogen receptor gene polymorphisms across all studied groups.
- The strongest observed associations between specific SNPs and E2 levels explained a small proportion (<4%) of the total variation.
- Further research may be needed to identify other genetic or environmental factors influencing E2 levels.
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