Comprehensive analysis of aromatase gene (CYP19A1) and estrogen receptor beta gene (ESR2) polymorphisms in female pattern hair loss

Abstract

Introduction: Female pattern hair loss (FPHL) is a complex polygenic trait in which sex steroid hormones may play a pathogenic role. No causative genes have been previously reported. It is unknown whether male androgenetic alopecia and FPHL are similar entities although both display a common pathognomonic feature of hair follicle miniaturisation1. The aromatase enzyme encoded by CYP19A1 converts androgens to estrogens in scalp hair follicles and is differentially expressed in balding and non-balding scalps of men and women2. Estrogenic effects in the hair follicle are regulated by the predominantly expressed estrogen receptor beta (ER-beta) encoded by ESR2. DNA sequence variation in CYP19A1 and ESR2 might influence the risk of developing FPHL. Method: In 484 women with grades 3-5 FPHL on the Sinclair scale and 471 controls we tested for associations between FPHL and DNA variation in and around the CYP19A1 and ESR2, using 61 and 32 tag single nucleotide polymorphisms (tag SNPs) respectively. Results: For CYP19A1, the CC genotype of the tag SNP rs4646 was found more frequently in women with FPHL (p = 0.006), especially in those <40 years who are considered the most genetically predisposed. Interestingly, the CC genotype of rs4646 has previously been associated with higher circulating estrogen levels3. For ESR2, the tag SNPs rs10137185 and rs17101774 showed significant associations with FPHL (p = 0.002 and p = 0.008, respectively) especially in those >40 years. Conclusions: Our findings suggest that at least 2 genes involved in sex hormone metabolism are implicated in the predisposition to FPHL.