Oestrogen receptor genetics: a needle that cuts through many haystacks?The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.

Abstract

Oestrogen is known to affect multiple aspects of human health, including complex traits such as cardiovascular disease, cancer, fracture risk, arthritis, behaviour and Alzheimer's disease. Oestrogen receptor α (ESR1), one of two known oestrogen activated transcription factors, is expressed throughout many tissues. It can regulate gene expression by both oestrogen-dependent and oestrogen-independent mechanisms that result in direct or indirect activation of transcription of a wide range of genes. Most of the hundreds of reports of ESR1 genetics published since 1990 have been in areas of cancer biology, bone mineral density, or fracture risk. In the past 3 or 4 years, however, there have been a handful of interesting reports of association of ESR1 polymorphism with cardiovascular disease, its established risk factors, or in relation to response to hormone replacement therapy.1–6 This recent literature, which was both particularly intriguing and inconclusive among women, provided a strong rationale for the investigation by Lawlor et al .7 These authors carried out a cross-sectional analysis of 3404 women from the British Women's Heart and Health Study. The women were in their 60s or 70s, from 23 towns across Britain; characterization included incident and prevalent coronary heart disease, its risk factors, and use of hormone replacement. Two single nucleotide polymorphisms from the first intron of ESR1 were genotyped in participant DNA samples. The polymorphisms, c454-397T>C and c454-351A>G , … *Corresponding author. fax: +1 617 253 5202. E-mail address : shearman{at}mit.edu