Association between estrogen receptor beta gene (ESR2) polymorphisms and female pattern hair loss – more evidence for a detrimental role for estrogens in hair growth

  • Dr Leona Yip, Departments of Medicine (Dermatology), The University of Melbourne and St Vincent’s Hospital Melbourne, Fitzroy, Victoria, Aus, Australia
  • Miss Sophie Zaloumis, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia, Australia
  • Dr Darryl Irwin, Sequenom, Inc., Herston, Brisbane, Australia, Australia
  • Dr Gianluca Severi, Cancer Epidemiology Center, The Cancer Council of Victoria, Carlton, Victoria, Australia, Australia
  • Prof Rod Sinclair, Departments of Medicine (Dermatology), The University of Melbourne and St Vincent’s Hospital Melbourne, Australia
  • Prof Stephen Harrap, Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia, Australia
  • Dr Justine Ellis, Murdoch Childrens Research Institute, Parkville, Victoria, Australia, Australia

Introduction: Female pattern hair loss (FPHL) is a complex polygenic trait in which sex steroid hormones may play a pathogenic role. We previously reported the aromatase gene, CYP19A1, as a putative causative gene for FPHL through a SNP association especially in affected women <40 years.1 This SNP association suggests a detrimental role for estrogens in hair growth through inference from a previously reported association between this particular SNP and higher circulating estrogen levels in post-menopausal women. Estrogen binding to ER-β, the predominant estrogen receptor subtype within the hair follicle, is thought to directly modulate hair growth. To further investigate the role of estrogens in FPHL, this study comprehensively examined ESR2 DNA sequence variation and their relationship with FPHL.
Method: In 484 women with grades 3-5 FPHL on the Sinclair scale and 471 controls, we tested for associations between FPHL and 32 tag SNPs that captured105 individual SNPs in and around the ESR2 gene region.
Results: The CC genotype of the associated tag SNP rs10137185 occurred more frequently in women with FPHL (OR = 0.52, 95% CI = 0.34 - 0.8, p = 0.003), especially in those ≥40 years. For the second associated tag SNP rs17701774, its TT genotype occurred more frequently in women with FPHL (OR = 0.32, 95% CI = 0.13 - 0.76, p = 0.008, age-adjusted), especially in those ≥40 years.
Conclusions: The association between ESR2 and FPHL further enhances our hypothesis that estrogens are pathogenic for FPHL. While CYP19A1 might predispose more to younger-onset FPHL, ESR2 might predispose to older-onset FPHL.

References:
1. Yip L, Zaloumis S, et al. Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss. Br J Dermatol. 2009; 161: 289-94.