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Genetics of Male Pattern Baldness

BY: Chandra Kala | Category: Genetics | Submitted: 2012-09-19 08:43:18
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Article Summary: "Hair loss is the nightmare for men and women globally. Baldness in men is generally hereditary, which is associated with chromosome X. Recent research on male pattern baldness has been proved not only allosome, autosomes also plays a role in Hair loss. This article gives brief summary on the genes and pathways associated with .."

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Hair loss is the nightmare for men and women globally. There are several factors that influence hair loss like nutrition, environment, stress and Hereditary. On the onset of puberty, especially men notice gradually thinning of hair in the head scalp. Genetically men have two types of hair follicles, first kind which is genetically programmed not to fall and second type which are affected by the process of baldness. Hair transplant technique much depends on the hair follicles which are not programmed to fall. There are several types of baldness depending on the area of loss of hairs on scalp. The hair loss due to environment, food and other types can be reversed with adequate care and treatment, while the hereditary hair loss is irreversible. Iron deficiency causes anemia which results in hair loss can be rectified by supplementing iron with the food take, while hereditary hair fall can only be rectified with hair transplant methods.

Androgenic alopecia (AGA) is one of the common hair loss types, which affects men and is caused due to androgen receptor pathway. Nearly 80% of observed AGA is hereditary. Androgenic alopecia other way known as male pattern baldness onset may also influence other diseases such as coronary heart disease (CVD), prostate cancer and metabolic syndrome. The androgen receptor pathway is triggered by androgen receptor, which is a member of hormone dependent nuclear transcription factors. Androgen receptor plays a key role in prostate cancer disease progression. Polymorphisms in the Androgen receptor and change in expression patter of the receptor are the main reasons for male baldness.

Several pathways are involved in Hair follicle stimulation and regenerations. Androgen receptor pathway is the critical pathway in determining the hair follicle regeneration and maintenance. Wnt/beta-catenin pathway helps in the hair follicle development and formation. Wnt pathway also stimulates hair follicles growth by expressing genes required for hair growth cycle. Androgen receptor and Wnt/beta-catenin pathway shows cross-talk and have opposite effect on hair follicle development. Transforming growth factor beta (TGFB1) pathway inhibits keratinocytes proliferation. Proliferating keratinocytes differentiates in to two out of three components of hair follicles which are hair shaft and inner root sheath (IRS). The third component of hair follicles is outer root sheath (ORS) which is outer layer of cells that envelops IRS and hair shaft. Bone morphogenetic protein (BMP) pathway inhibits hair follicle cycle progression and hence has a positive effect on hair loss. Signal transducer and activator of transcription (STAT) pathway also has influence on hair follicles. Sonic hedgehog (Shh) and lymphoid enhancer-binding factor 1 (Lef-1) pathways are also important in activating hair shaft formation. Tumor Necrosis Factor (TNF) pathway has a role in hair growth cycle since patients having anti-TNF treatment for rheumatic diseases have reported hair loss. Radiation used in cancer treatment causes hair loss by increasing reactive oxygen species (ROS) of the cell and triggering ROS pathway.

Hair loss pattern was earlier known to be inherited from maternal side and genes on chromosome X were associated with baldness. Apart for allosome, now autosomes are also involved in male pattern baldness. Genome Wide Associations Studies (GWAS) have revealed genes involvement in AGA like Forkhead fox A2 (FOXA2), intramembrane protease 5 (IMP5), microtubule-associated protein tau (MAPT), histone deacetylase 4 and 9 (HDACs), autism susceptibility candidate 2 (AUTS2), Androgen receptor (AR) and many more genes. The major genes that are involved male baldness are located on chromosome 17, 20 and X. Several Single Nucleotide Polymorphisms (SNPs) are shown to be associated with androgenic alopecia. GWAS studies throw insights on the associations of other diseases from the onset of male baldness.

Baldness phenomenon is associated with negative personality perceptions among men and women that lead to medical therapy running in billions and a major pharmaceutical area of drug sales and research. There are several forms of medicines available for treatment of baldness ranging from herbal oils to pharmaceutical drugs. The treatment for baldness through drugs will be effective only when genetics of the individual is studied thoroughly through next generation sequencing (NGS) method. Alternatively, hair transplant has fewer side effects than drugs used for treatment of baldness. The drawback of hair transplant is the cost of surgery which the patient has to pay. More research is required to make more affordable treatments for baldness, which will benefit billions of men and women.

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