Male and Female Pattern Hair Loss: Gene Driven but Not Your Genetic Fate

Androgenetic alopecia-male- and female-pattern hair loss-is known to have a genetic basis. It is an inheritable condition, commonly described as "running in the family". (See About Hair Loss). Having close family members with androgenetic alopecia significantly increases your risk for having some degree of hair loss between adolescence and middle age. How much hair you will lose and in what pattern it is lost is not predictable with 100% accuracy, but family patterns of hair loss are fairly reliable in forecasting both degree and pattern of an individual's androgenetic alopecia. Family history of hair loss is one of the important questions a physician hair restoration specialist will ask in consultation with a new patient.

Whether or not you consult a physician hair restoration specialist about hair loss, you may already have asked yourself a question: If you have androgenetic alopecia in your immediate family (father, mother, aunts, uncles, grandparents), is hair loss due to androgenetic alopecia your genetic fate?

The answer is YES if you are willing to accept your hair loss, or consider hair loss as one of the prices you pay for living.

The answer is NO if you decide that you will not accept your hair loss, turning instead to consultation with a physician hair restoration specialist about increasingly successful medical and surgical approaches to hair restoration.

Genes and Genetic Fate

The dream of treating gene-associated or gene-caused conditions by gene manipulation is yet to be realized. Understanding of the "genetic code" is advancing rapidly; however, understanding has not yet produced the ability to manipulate genes to treat or prevent disease or conditions such as androgenetic alopecia.

Although gene-associated or gene-caused conditions are not yet treatable at the genetic level outside of the investigational setting, it is increasingly possible to identify genetic predisposition to a pathologic condition, and take steps to modify the physical impact of the condition. Medical genetics is acquiring the knowledge and technology to provide clinically significant information about a widening spectrum of gene-associated or gene-caused conditions. This is knowledge that can be used to avoid a "genetic fate".

Beginning in the 1960s, geneticists began to identify diseases linked to a single gene defect-for example, phenylketonuria which was a cause of severe mental retardation. The knowledge quickly led to development of neonatal testing for the genetic defect that causes phenylketonuria-a condition that caused cells to accumulate an excess of the chemical phenylalanine, which is a constituent of many processed foods. Neonatal testing allowed parents of children who carried the genetic defect to make sure that the children avoided consumption of foods containing phenylalanine. Avoidance of phenylalanine prevented development of the disease and what would otherwise have been the child's "genetic fate".

Medical genetics is rapidly evolving from its capacity to identify single-gene disorders such as phenylketonuria and cystic fibrosis, and single-chromosome disorders such as Down syndrome, toward understanding of multiple-gene and gene-environment interactions associated with complex conditions such as cardiovascular disease, diabetes, asthma and cancers.

The genetically complex conditions are often recognized to "run in families", but may not be identified with known mutations (permanent, transmissible changes in a gene). Genetic mutations are often subtle, and there may be subtle, disease-associated interactions between genes and environmental factors such as tobacco smoke, industrial chemicals, air pollution and diet. Certain forms of heart disease are known to "run in families", and current approaches to prevention (avoidance of genetic fate) stress modification of gene-environment interactions by means of cholesterol-lowering diets and medications.

The specific genes involved in growth of scalp hair are net yet identified with certainty, but many investigators are pursuing the answer. Identification of hair-growth genes will not immediately lead to genetic therapy for hair loss. The road from gene-identification to clinical application of the knowledge can require years of additional laboratory work and clinical trials.

Androgenetic alopecia, however, is one gene-caused condition that does not have to wait for gene therapy to overcome its physical impact. Medical approaches to slowing hair loss and stimulating new hair growth have a relatively good degree of success (See Medical Treatments). Surgical approaches-hair transplantation, alopecia reduction, hair-bearing flap transfer-are highly successful in overcoming the cosmetic defects of hair loss (See Surgical Treatments).

Other Gene-Linked Causes of Hair Loss

Androgenetic alopecia is the best known and most widely distributed gene-caused or gene-associated cause of hair loss. There are a number of other causes of hair loss with a known or suspected genetic link:

  • Alopecia areata (See About Hair Loss) has a hereditary component and is often seen in association with other conditions such as autoimmune disease and Down syndrome. Alopecia areata is often classified as an autoimmune condition. Patterns of inheritance have been identified. Multiple-gene mutations and/or gene/environment interactions have been suggested as the underlying cause of alopecia areata.
  • Congenital alopecia is total or partial absence of hair beginning at birth or infancy. A pattern of genetic inheritance has been identified, but no specific genetic mutations.
  • Hypotrichosis is a condition where hair is sparse, brittle and lacking sufficient pigment. It is often seen in association with other conditions that result in physical deformity or mental retardation. A pattern of genetic inheritance has been identified, but no specific genetic mutations.
  • Circumscribed alopecias are conditions of hair loss in circumscribed areas of the scalp associated with various forms of skin defect. Familial patterns of inheritance have been noted.
  • Hair shaft abnormalities result in brittle, broken, beaded, twisted, knotted and weathered-appearing hair. Familial patterns of inheritance have been identified for many of these conditions, but no specific genetic mutations are yet identified.

Hair loss due to alopecia areata or other gene-linked conditions cannot be "cured" at the genetic level, but cosmetic defects resulting from hair loss can often be successfully treated. The essential starting point for successful treatment is correct diagnosis of the cause of hair loss by a physician hair restoration specialist. Correct diagnosis points the way to appropriate treatment by hair restoration medications, hair restoration surgery, or full-scalp or partial-scalp hair prostheses.

Will gene-caused or gene-associated hair loss ever be curable by gene manipulation? The success of the Human Genome Project opened the first door on the possibility of gene manipulation. Other doors remain to be opened:

The Human Genome Project: It's a Starting Point in Gene Therapy

Hopes for deeper understanding of gene-caused and gene-associated conditions were lifted by the "breaking" of the human genetic code in the Human Genome Project. The Human Genome Project was a phenomenal success. But, even as the Human Genome Project was underway, investigators began to recognize that an extra set of instructions-aside from the so-called genetic code-can influence gene activity without altering the DNA sequence in genes. This extra set of instruction has been given the name "epigenetics" or "epigenetic code". It is much more subject to environmental influences than the DNA code; it is often by means of the epigenetic code that factors such as diet, smoking, toxins, etc., influence susceptibility to disease. Investigators understand how the epigenetic code influences gene activity without altering DNA sequence; the very broad influence of the epigenetic code in human disease is gradually being better understood.

The Human Genome Project is also being followed up by another essential investigation of the human genome-the International Haplotype Map Project, usually shortened to "The HapMap Project". The Human Genome Project laid out an atlas of the human genome-how many genes we carry and where they are located on the human genome. But, knowing the location of genes on the genome is only an initial step in linking the human genome to human disease. The genome is not static. Gene expression is influenced by constant changes taking place along the genome-for example, by copy number variation, insertion/deletion of genetic instructions, structural alteration, and by changes in DNA known as single nucleotide polymorphisms (SNPs).

SNPs may influence gene function, but the influence of many identified SNPs has yet to be understood. Because SNPs are inherited along with the genes on which they occur, a map of these inherited genetic variations will be enormously helpful in identifying their largely uncharacterized role in human disease. The HapMap Project was created to put together such a map.

What is a "haplotype"? Individuals who carry a SNP on a gene at one chromosomal location often carry predictable specific "SNP genes" at other nearby sites. (Chromosomes are the thread-like structures in the cell that carry DNA). When a new SNP arises, the change is identified with a chromosome site at which it occurred. A particular combination of "SNP genes" along a chromosome is called a haplotype.

The HapMap, when completed, will help guide better understanding of the role of genetic variations in human disease.

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