Investigation of four novel male androgenetic alopecia susceptibility loci: no association with female pattern hair loss

Abstract

Female pattern hair loss (FPHL) is a common hair loss disorder in women and has a complex mode of inheritance. The etiopathogenesis of FPHL is largely unknown; however, it is hypothesized that FPHL and male pattern baldness [androgenetic alopecia (AGA)] share common genetic susceptibility alleles. Our recent findings indicate that the major AGA locus, an X-chromosome region containing the androgen receptor and the ectodysplasin A2 receptor (EDA2R) genes, may represent a common genetic factor underlying both early-onset FPHL and AGA. This gives further support for the widespread assumption of shared susceptibility loci for FPHL and AGA. However, we could not demonstrate association of further AGA risk loci, including 20p11, 1p36.22, 2q37.3, 7p21.1, 7q11.22, 17q21.31, and 18q21.1, with FPHL. Interestingly, a recent study identified four novel AGA risk loci in chromosomal regions 2q35, 3q25.1, 5q33.3, and 12p12.1. In particular, the 2q35 locus and its gene WNT10A point to an as-yet unknown involvement of the WNT signaling pathway in AGA. We hypothesized that the novel loci and thus also the WNT signaling may have a role in the etiopathogenesis of FPHL and therefore examined the role of these novel AGA risk loci in our FPHL samples comprising 440 German and 145 UK affected patients, 500 German unselected controls (blood donors), and 179 UK supercontrols. Patients and controls were genotyped for the top two single nucleotide polymorphisms at each of the four AGA loci. However, none of the genotyped variants displayed any significant association. In conclusion, the results of this study provide no support for the hypothesis that the novel AGA loci influence susceptibility to FPHL.

Towards a consensus on how to diagnose and quantify female pattern hair loss – The ‘Female Pattern Hair Loss Severity Index (FPHL‐SI)’

“…[25][26][27][28][29][30][31][32][33][34][35] However, convincing genetic loci linked to FPHL remain to be identi-fied, and the potentially important impact of epigenetic factors on FPHL awaits systematic exploration. [25][26][27][28][29][30][31][32][33][34][35] However, convincing genetic loci linked to FPHL remain to be identi-fied, and the potentially important impact of epigenetic factors on FPHL awaits systematic exploration.…”

“…The familial occurrence of FPHL 24 renders linkage to defined susceptibility genes likely, which may well be different from those identified for androgenetic alopecia in males. [25][26][27][28][29][30][31][32][33][34][35] However, convincing genetic loci linked to FPHL remain to be identi-fied, and the potentially important impact of epigenetic factors on FPHL awaits systematic exploration. 21,25,[36][37][38][39][40][41] The epidemiology of FPHL remains unclear and partially contradictory (see below), likely as a reflection of major variations in the populations examined, the inherent ethnic diversity of hair and the techniques by which a diagnosis of FPHL was reached.…”

Forensic DNA Phenotyping: Predicting human appearance from crime scene material for investigative purposes

“…Early-onset female pattern hair loss (FPHL), which is much more rare than male pattern baldness, seem to share some genetic basis with the male form, such as the X-chromosomal region containing the AR and EDA2R genes [66]. However, various other genes associated with AGA do not seem to be involved in FPHL [67], leaving the aetiology of female hair loss largely unknown as of yet.…”

Molecular Genetics of Alopecias

“…Although it was previously postulated that AGA and FPHL share a common genetic background [63][64][65], several recent studies examining the known AGA-associated loci in large FPHL cohorts have shown no association of some of these loci with FPHL [66,67].…”