Gene-wide association study between the aromatase gene (CYP19A1) and female pattern hair loss

Background Female pattern hair loss (FPHL) is a common trait in which androgens and oestrogens may have a pathogenic role. The aromatase enzyme converts androgens to oestrogens in scalp hair follicles and is differentially expressed in balding and nonbalding scalps of women. Sequence variation in the gene encoding aromatase, CYP19A1, might influence the risk of developing FPHL. Objectives To examine the role of CYP19A1 genetic variation in the heritability of FPHL. Methods We investigated associations between FPHL and 61 tag single nucleotide polymorphisms (SNPs) representing variation in and around CYP19A1 in 484 caucasian women with grades 3-5 FPHL on the Sinclair scale, and 471 caucasian women with no evidence of hair loss. Results For the tag SNP rs4646 (overall genotype frequencies: CC, 53æ6%; AC, 39æ3%; AA, 7æ1%), the genotype CC was more frequent in women with FPHL (58æ1%) than controls (48æ9%) (P = 0æ006). Although this result did not achieve experiment-wide significance (P< 0æ001 by permutation testing), subanalyses according to sources of recruitment and ages at presentation revealed consistent patterns of association. In particular, young cases (< 40 years) had the highest frequency of the CC genotype (68æ2%) among all subgroups. Conclusions These findings suggest that the common rs4646 C allele, which has been associated previously with higher circulating oestrogen levels, might be associated with predisposition to FPHL.