|?|| (A;A) (A;C) (C;C) ||28|
rs9287638 is located on chromosome 2q37 and lies downstream of the gene, HDAC4. HDAC4 is part of histone deactelyases enzyme class that deacteylates nucleosomal histones, thus acting as transcriptional correpresors. This SNP is associated with increased risk of androgenic alopecia (AGA). [PMID 22693459] . Androgenic alopecia (male pattern baldness) affects up to 70% of men. Androgens especially dihydrotesterone (DHT) plays a key role in androgenic alopecia. With ageing, androgens reduces hair growth on the scalp and temples but leads to increased hair growth on the face. This phenomena is referred to as the androgen paradox [PMID 23016593]
Androgenic alopecia has an estimated heritability of 80% and is a polygenic trait. The strongest effect is seen with the X-chromosomal androgen receptor/ectodysplasin A2 receptor locus (AR/EDA2R). [PMID 23358095]. Rs2497938 in the AR gene (T) risk allele is 2.2 (CI: 2.04-2.37, p=2x10^-91). [PMID 22693459]
The first GWAS looking at androgenic alopecia had 578 cases and 547 controls and identified rs6625163 in the AR gene (A) risk allele with odds ratio of 3.3 (CI:2.31-4.71, p=5x10^-11) as well as rs1160312 in the PAX1 gene (A) risk allele with odds ratio of 1.6 (CI:1.42-1.80,p=1x10^-14).
[PMID 18849991]. Subsequent studies validated that SNPs in PAX1 and AR increased risk of developing androgenic alopecia [[https://www.ncbi.nlm.nih.gov/pubmed/18849994
?dopt=Abstract PMID 18849994
Using a large-scale meta-analysis of seven GWAS studies for early onset AGA in 12,806 European men, 6 novel susceptibility loci were identified and rs9287638 had the lowest p-value at 1.01 x 10^-12. rs2073963, in the HDAC9 gene, was also associated with AGA. Both HDAC4 and HDAC9 were well expressed in hair follicles. HDAC4 was found to be expressed in skin and scalp, but HDAC9 was expressed in neither. [PMID 22693459]
HDAC4 has been shown to interact with transcription factors ARR19 & CRIF1, thereby inhibiting Androgenic Receptor (AR) transactivation.
AR is a steroid receptor and is responsible for effecting transcriptional changes upon binding with androgens within the cell. However, the role of androgen-AR complex in effecting androgenic alopecia is not understood [PMID 14576337] HDAC4 could influence pathogenesis of androgenic alopecia through dysregulation of the androgen pathway. [PMID 22693459]
New studies have identified more risk alleles in autosomal chromosomes such as rs9287638 in chromosome 2. These new discoveries allow for further understanding of the pathobiology underlying androgenic alop
[PMID 22693459] Six Novel Susceptibility Loci for Early-Onset Androgenetic Alopecia and Their Unexpected Association with Common Diseases