AR

The AR gene provides instructions for making a protein called an androgen receptor. Androgens are hormones (such as testosterone) that are important for normal male sexual development before birth and during puberty. Androgen receptors allow the body to respond appropriately to these hormones. The receptors are present in many of the body's tissues, where they attach (bind) to androgens. The resulting androgen-receptor complex then binds to DNA and regulates the activity of androgen-responsive genes. By turning the genes on or off as necessary, the androgen receptor helps direct the development of male sexual characteristics. Androgens and androgen receptors also have other important functions in both males and females, such as regulating hair growth and sex drive.

In one region of the AR gene, a DNA segment known as CAG is repeated multiple times. This CAG segment is called a triplet or trinucleotide repeat. In most people, the number of CAG repeats in the AR gene ranges from fewer than 10 to about 36.

androgen insensitivity syndrome - caused by mutations in the AR gene

More than 600 different mutations in the AR gene have been identified in people with androgen insensitivity syndrome. Most of these mutations are changes in single DNA building blocks (base pairs). Other mutations insert or delete multiple base pairs in the gene or affect how the gene is processed into a protein. Some changes in the AR gene lead to an abnormally short version of the androgen receptor protein; others result in the production of an abnormal receptor that cannot bind to androgens or to DNA. As a result, cells that are sensitive to androgens become less responsive to these hormones or unable to use these hormones at all.

Mutations that completely eliminate the function of the androgen receptor cause complete androgen insensitivity syndrome. Genetic changes that significantly reduce but do not eliminate the receptor's activity cause partial androgen insensitivity syndrome. Mild androgen insensitivity syndrome results from changes that only slightly reduce the activity of the receptor.

spinal and bulbar muscular atrophy - caused by mutations in the AR gene

Spinal and bulbar muscular atrophy results from an expansion of the CAG trinucleotide repeat in the AR gene. In people with this disorder, CAG is abnormally repeated from 38 to more than 60 times. Although the extended CAG region changes the structure of the androgen receptor, it is unclear how the altered protein disrupts nerve cells. Researchers believe that a fragment of the androgen receptor protein containing the CAG repeats accumulates within these cells and interferes with normal cell functions. This buildup leads to the gradual loss of nerve cells in the brain and spinal cord that control muscle movement.

androgenetic alopecia - associated with the AR gene

Alterations in the AR gene are associated with an increased risk of androgenetic alopecia (also known as male-pattern baldness in men and female-pattern baldness in women). The variations result from small changes in the number or types of DNA building blocks (base pairs) that make up the AR gene. These genetic changes appear to be most frequent in men with hair loss that begins at an early age. Researchers believe that AR gene variations may increase the activity of androgen receptors in the scalp. Although androgenetic alopecia is related to the effects of androgens on hair growth, it remains unclear how changes in the AR gene increase the risk of patterned hair loss in men and women with this condition.

breast cancer - associated with the AR gene

Researchers have considered a possible relationship between the length of the CAG repeat region in the AR gene and a woman's chance of developing breast cancer. The results of research studies have been mixed. Some studies have suggested that a long CAG repeat region is associated with an increased risk of breast cancer in women, and that a shorter CAG repeat region is associated with a reduced risk. Other research indicates that a shorter CAG repeat region may be related to an increased risk of both breast cancer and noncancerous (benign) breast disease. Shorter CAG repeat regions have also been associated with more aggressive forms of breast cancer. Additional research is needed to clarify what role, if any, this region of the AR gene plays in determining breast cancer risk.

other cancers - associated with the AR gene

At least 85 mutations in the AR gene have been associated with prostate cancer. Almost all of these mutations are somatic, which means they develop during a person's life and occur only in certain cells (in this case, cells in the prostate). Somatic mutations are not inherited and are not passed to future generations.

Some studies have shown an increased risk of prostate cancer in men with a short CAG repeat region in the AR gene; however, other studies did not find this connection. Researchers also believe that extra copies of the gene in cancer cells may be associated with the progression of prostate cancers.

Recent studies have also suggested that a longer CAG repeat region in the AR gene may increase the risk of endometrial cancer in women.