Genetic Variation in the Human Androgen Receptor Gene Is the Major Determinant of Common Early-Onset Androgenetic Alopecia

Abstract

Androgenetic alopecia (AGA), or male-pattern baldness, is the most common form of hair loss. Its pathogenesis is androgen dependent, and genetic predisposition is the major requirement for the phenotype. We demonstrate that genetic variability in the androgen receptor gene (AR) is the cardinal prerequisite for the development of early-onset AGA, with an etiological fraction of 0.46. The investigation of a large number of genetic variants covering the AR locus suggests that a polyglycine-encoding GGN repeat in exon 1 is a plausible candidate for conferring the functional effect. The X-chromosomal location of AR stresses the importance of the maternal line in the inheritance of AGA.

Androgen Receptor Gene Tagging Single Nucleotide Polymorphisms are not Associated with Polycystic Ovary Syndrome in South Indian Women

“…In contrast to African population like Yoruba in Ibadan, Nigeria (YRI) showed the complete absence of wild homozygous genotype (T/T) and the presence of wild homozygous (C/C), but seems to be polymorphic in other African populations like Maasai in Kinyawa, Kenya (MKK) and African ancestry in Southwest USA (ASW) and European population like Utah residents with Northern and Western European ancestry from the CEPH collection (CEU). SNP rs5919393 (C/T) found to be associated with endometrial cancer [25], and androgenetic alopecia in European population [26]. However, SNP rs5919393 is found to be monomorphic in Chinese population [27] and in the present study (Table 2).…”

Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men

“…An increased risk of prostate cancer has been associated with a short number (25,26) or high number (27) of GGN repeats. The most common allele has been reported to be correlated with androgenic baldness, while 24 GGN repeats seemed to have a protective role (13). Lower semen volumes were found in men with GGN lengths shorter than 23 (14).…”

“…Considerable discrepancies exist between the findings of the in vitro studies analyzing the effect of different GGN repeat lengths on AR activity in various cell cultures (7)(8)(9)(10)(11). Nevertheless, several epidemiological studies have suggested a significant, albeit modest, impact of the repeat on clinical androgenic effects; the GGN repeat has been linked to the risk of prostate cancer (12), to alopecia (13), spermatogenesis (14), occurrence of hypospadia (15), and breast cancer (16).…”

Addressing Androgenetic Alopecia-A Complex Disorder-with a Multilateral Treatment Strategy

“…For instance the AR polymorphism, Stu 1 is prominently associated with AGA. 8 Additionally, the 5α-reductase, aromatase and estrogen receptor genes may contribute to occurrence of AGA. 9 Via the action of 5α-reductase, systemic testosterone is converted to dihydrotestosterone (DHT).…”