- Reaction score
- 320
http://www.ijdvl.com/article.asp?is...=3;spage=263;epage=268;aulast=Martinez-Jacobo
-> The stem cells of the hair follicle are located in the bulge where they periodically alternate between activated and quiescent phases to maintain the stem cell population and produce new hair follicles. Wang et al. noted that when murine hair follicle stem cells were active, the FOXC1 gene was highly expressed, maintaining stem cell adhesion and promoting transition to the quiescent state. It also activates the signaling of Nfatc1 and bone morphogenetic proteins, which play a role in the maintenance and development of hair follicles
-> Torkamani et al. found that the arrector pili muscle degenerates and is replaced by adipose tissue in androgenetic alopecia
-> The role of microinflammation in the pathogenesis of androgenetic alopecia has been investigated by Jaworsky et al.who showed that the inflammatory cell infiltrate in the follicular bulge produces a progressive fibrosis of the perifollicular zone resulting in injury to follicular stem cells, impairment of normal hair cycling and finally, hair loss
-> Recent genome-wide association studies in Androgenetic Alopecia have identified strong association signals in the X chromosome. Both the AR gene and the ectodysplasin A2 receptor (AR/EDA2R locus in Xq11-q12) showed strong signals for Androgenetic Alopecia
-> There is evidence that both 5-alpha reductase enzymes and the androgen receptor are highly expressed in balding follicles as compared with nonbalding follicles on the same scalp
-> It has been estimated that the AR gene may confer up to 40% of the total genetic risk, which is considered a high level of risk for a single gene.
-> They identified four risk loci for androgenetic alopecia located in 2q35, 3q25.1, 5q33.3 and 12p12.1. The strongest association signal was observed in 2q35 (P = 3.33 × 10-15). This locus contains the WNT10A gene, which is expressed in the bulge during the anagen phase of the hair growth cycle and has been shown to have a genotypic effect on hair follicle expression
-> A meta-analysis by Li et al. identified 6 new risk loci for androgenetic alopecia in 1p36.22, 2q37, 7p21.1, 7q11.22, 17q21.31 and 18q21.1 and a strong association for androgenetic alopecia in 20p11 and the AR gene.
The risk locus for androgenetic alopecia at 20p11 had earlier been identified by Liang et al. in a Chinese population.
A risk locus at 3q26 was identified in a German population
and a polymorphism in the APCDD1gene (Wnt signaling inhibitor) located in 18p11.2 has been also been associated with androgenetic alopecia
The identification of a new susceptibility autosomal gene in these autosomal loci suggests that nonandrogen-dependent pathways are also involved in androgenetic alopecia pathogenesis
-> Relatively few studies have used expression analyses because of difficulties in obtaining scalp biopsies. Various genes such as BMP2, ephrinA3, PGDS, PGD2, BDNF, neurotrophin-3 protein, neural growth factor-β, ASS1 and GSN have been found to be differentially expressed in dermal papilla cell culture and scalp biopsy samples from patients with androgenetic alopecia.
-> Mirmirani et al. identified 38 differentially expressed genes between the scalp vertex and frontal regions of 16 patients with androgenetic alopecia. Among the overexpressed genes were MSL3L2, CD209, MUC7, SLC6A14 and ANKRD20B. The subexpressed genes included DUSP1, FOS, FOSB, CYR61, HBB, EGR1, ZFP36, MS4A1, IGLI3, ATF3, PSG3, EFCAB4B, KRTAP as well as various noncoding RNAs. These authors suggest a specific expression signature for these two regions
-> The Notch signaling pathway is also involved in androgenetic alopecia. Midorikawa et al. found that increased androgen levels resulted in a negative feedback of gene expression of the Notch pathway, leading to miniaturization of the hair follicle and overexpression of the AR gene. Both the Notch and the Wnt pathways are directly affected by androgen expression in androgenetic alopecia.
-> DNMT1 is involved in the establishment and regulation of methylation patterns for tissue-specific cytokines, suggesting that the activity of this gene may be relevant for the development of androgenetic alopecia.
-> The stem cells of the hair follicle are located in the bulge where they periodically alternate between activated and quiescent phases to maintain the stem cell population and produce new hair follicles. Wang et al. noted that when murine hair follicle stem cells were active, the FOXC1 gene was highly expressed, maintaining stem cell adhesion and promoting transition to the quiescent state. It also activates the signaling of Nfatc1 and bone morphogenetic proteins, which play a role in the maintenance and development of hair follicles
-> Torkamani et al. found that the arrector pili muscle degenerates and is replaced by adipose tissue in androgenetic alopecia
-> The role of microinflammation in the pathogenesis of androgenetic alopecia has been investigated by Jaworsky et al.who showed that the inflammatory cell infiltrate in the follicular bulge produces a progressive fibrosis of the perifollicular zone resulting in injury to follicular stem cells, impairment of normal hair cycling and finally, hair loss
-> Recent genome-wide association studies in Androgenetic Alopecia have identified strong association signals in the X chromosome. Both the AR gene and the ectodysplasin A2 receptor (AR/EDA2R locus in Xq11-q12) showed strong signals for Androgenetic Alopecia
-> There is evidence that both 5-alpha reductase enzymes and the androgen receptor are highly expressed in balding follicles as compared with nonbalding follicles on the same scalp
-> It has been estimated that the AR gene may confer up to 40% of the total genetic risk, which is considered a high level of risk for a single gene.
-> They identified four risk loci for androgenetic alopecia located in 2q35, 3q25.1, 5q33.3 and 12p12.1. The strongest association signal was observed in 2q35 (P = 3.33 × 10-15). This locus contains the WNT10A gene, which is expressed in the bulge during the anagen phase of the hair growth cycle and has been shown to have a genotypic effect on hair follicle expression
-> A meta-analysis by Li et al. identified 6 new risk loci for androgenetic alopecia in 1p36.22, 2q37, 7p21.1, 7q11.22, 17q21.31 and 18q21.1 and a strong association for androgenetic alopecia in 20p11 and the AR gene.
The risk locus for androgenetic alopecia at 20p11 had earlier been identified by Liang et al. in a Chinese population.
A risk locus at 3q26 was identified in a German population
and a polymorphism in the APCDD1gene (Wnt signaling inhibitor) located in 18p11.2 has been also been associated with androgenetic alopecia
The identification of a new susceptibility autosomal gene in these autosomal loci suggests that nonandrogen-dependent pathways are also involved in androgenetic alopecia pathogenesis
-> Relatively few studies have used expression analyses because of difficulties in obtaining scalp biopsies. Various genes such as BMP2, ephrinA3, PGDS, PGD2, BDNF, neurotrophin-3 protein, neural growth factor-β, ASS1 and GSN have been found to be differentially expressed in dermal papilla cell culture and scalp biopsy samples from patients with androgenetic alopecia.
-> Mirmirani et al. identified 38 differentially expressed genes between the scalp vertex and frontal regions of 16 patients with androgenetic alopecia. Among the overexpressed genes were MSL3L2, CD209, MUC7, SLC6A14 and ANKRD20B. The subexpressed genes included DUSP1, FOS, FOSB, CYR61, HBB, EGR1, ZFP36, MS4A1, IGLI3, ATF3, PSG3, EFCAB4B, KRTAP as well as various noncoding RNAs. These authors suggest a specific expression signature for these two regions
-> The Notch signaling pathway is also involved in androgenetic alopecia. Midorikawa et al. found that increased androgen levels resulted in a negative feedback of gene expression of the Notch pathway, leading to miniaturization of the hair follicle and overexpression of the AR gene. Both the Notch and the Wnt pathways are directly affected by androgen expression in androgenetic alopecia.
-> DNMT1 is involved in the establishment and regulation of methylation patterns for tissue-specific cytokines, suggesting that the activity of this gene may be relevant for the development of androgenetic alopecia.