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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2007

Open Access 01-12-2007 | Research article

Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study

Authors: Maria Nilsson, Ingrid Dahlman, Hong Jiao, Jan-Åke Gustafsson, Peter Arner, Karin Dahlman-Wright

Published in: BMC Medical Genetics | Issue 1/2007

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Abstract

Background

The estrogen receptors α and β (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes.

Methods

23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression.

Results

No ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value < 0.01 were genotyped in a second cohort where no association with obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009–0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction.

Conclusion

ESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor agonists implies that low adipose tissue ESR1 levels attenuate catecholamine resistance in sc fat cells of obese women hereby contributing to loss of sc and gain of visceral fat. There is no evidence for a genetic impact of ESR1 on lipolysis or lipogenesis.
Appendix
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Metadata
Title
Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study
Authors
Maria Nilsson
Ingrid Dahlman
Hong Jiao
Jan-Åke Gustafsson
Peter Arner
Karin Dahlman-Wright
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2007
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-8-73

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