Thursday, February 28, 2008

Untangling the Genetics of Hair Loss

If you have male pattern baldness, you've probably heard that either your mother's father or your father's father is to blame. But before you start resenting one of your dear grandfathers, you should know that this piece of misinformation is derived from a study that is almost 100 years old. New studies and a more through understanding of the human genome confirm that male and female pattern baldness is a complex genetic trait.

"There is evidence that [male and female pattern baldness] is genetically based, but we don't know the inheritance pattern," says Animesh A. Sinha, MD, PhD, an assistant professor of dermatology at Weill Medical College of Cornell University in New York City who studies the genetics and immunology of complex skin disease. "We do know that it's not likely to be due to one gene or one gene mutation: it's likely to be due to multiple genes."

To understand male and female pattern baldness, it helps to understand the hair growth cycle, which is divided into three phases: the growth phase, the involution, or regression, phase and the resting phase. As Barry I. Resnik, MD, a dermatologist in private practice in Aventura, Florida and an assistant clinical professor of dermatology and cutaneous surgery at the University of Miami School of Medicine, explains, "In hair loss, the sleeping phase gets longer and the growing phase gets shorter until it goes to sleep. This is mediated, in part, by increasing amounts of, and/or increasing sensitivity to, active male hormone, dihydrotestosterone (DHT)." As a result of this altered growth cycle, hair shafts become shorter and thinner, a process called follicular miniaturization.

It's unclear what is happening genetically to bring about miniaturization. As Dr. Sinha says, "We don't know what genes are involved; how many there are; or how the genes interact with themselves or with environmental factors."

To address these issues, large-scales studies of families are needed. Such studies would involve people with pattern hair loss and their siblings, as well as people without hair loss who can be used as controls. All study participants would be screened for genetic mutations, or changes, that might be linked to hair loss. The identification of such changes would help scientists locate the genes responsible for pattern baldness.

Angela M. Christiano, PhD, an associate professor at Columbia University in New York City, has identified several genes in mice and humans that are involved in different forms of inherited alopecias. These discoveries may, at some future point, shed some light on the genetics of male and female pattern hair loss as well. Many scientists are hard at work to understand the role of genetics in normal hair growth and cycling, so that these basic principles can then be applied to the study of male and female pattern baldness.

Once the genes for male and female pattern baldness are identified, Dr. Sinha says, scientists can begin to look at how the condition evolves, because not everyone with a gene for a particular medical condition will develop that condition. For this to occur, the relevant genes must interact with each other and certain environmental, or outside, influences in a specific way, which, for now, remains unknown.

Dr. Sinha's lab is currently examining how genes express themselves in order to figure out the pathway that leads to alopecia areata, a type of sudden hair loss that affects children and adults. Thanks to new technologies such as the gene microarray, which allows scientists to look at thousands of genes at a time, identifying groups of genes and observing gene expression patterns is far easier than it was in the past.

"The ultimate goal of understanding the genetics of these conditions is to identify individuals at risk by designing a screening test." Dr. Sinha explains. "That way you can develop preventative therapies." Such a test would identify at-risk individuals by looking for a particular genetic pattern, or signature.

In the meantime, don't try to pin your hair loss on any one family member. Instead, spread the blame around. As Dr. Resnick explains, "The more members of the your family who have male pattern loss, the more likely you are to have it."