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Q: There was a retrospective study by Lotufo et al. linking male pattern baldness to heart disease. Do you think there are other links like this for androgenetic alopecia? — J.L., San Francisco, CA

A: Family studies revealed both the androgen receptor locus on the X chromosome, as well as a new locus on chromosome 3q26. Association studies performed in two independent groups revealed a locus on chromosome 20 (not near any known genes) as well as the androgen receptor on the X chromosome.

So far, the genetic studies for androgenetic alopecia (AGA) have not revealed identification of a particular gene other than the androgen receptor, as well as the two candidate regions on chromosomes 3 and 20. Inasmuch as the androgen receptor can be involved in other diseases, this might be a feasible connection. Until candidate genes are identified that underlie AGA, it is impossible to predict where the commonalities might lie.

Excerpted from Angela Christiano, Hair Transplant Forum International 2011; 21(1): 14-15.

Read more about Hair Loss Genetics, and see some other Hair Restoration Answers posts on the topic.

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CBS News - Hey, Baldy: 10 Things You Need to Know about Hair LossCBS News has enlisted the help of Dr. Bernstein in dispelling a series of myths which circulate in the general public about the causes and treatments of hair loss. The feature is titled, Hey, Baldy: 10 Things You Need to Know about Hair Loss.

Horseradish and pigeon droppings. That’s the magic hair-growth potion prescribed by Hippocrates. Alas, there are so many myths about hair loss that folks today are almost as clueless as the father of medicine.

Keep reading as hair loss expert Dr. Robert Bernstein, clinical professor of dermatology at Columbia University, explodes 10 all-too-common follicle fallacies…

Do hair loss genes come from the father’s side or the mother’s? Do bald men just have more testosterone in their system? Do women experience hair loss? Find Dr. Bernstein’s answers to these questions at the CBS News feature.

Visit our hair loss section where Dr. Bernstein debunks more hair loss myths.

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Dr. Eric S. Schweiger - Associate at Bernstein Medical - Center for Hair RestorationDr. Eric S. Schweiger, board-certified dermatologist, is quoted in a few recent articles on the effects of chemotherapy on hair, genetic testing for hair loss, and protecting a balding scalp from the sun.

“Coping with Chemo-Induced Hair Loss” was published in a recent issue of Energy Times, a publication focused on wellness and nutrition. Dr. Schweiger commented on the way hair follicles can react to chemotherapy treatment for cancer patients:

Expect changes like “chemo curl.” Eric Schweiger, MD, explains that chemo shocks rapidly dividing cells like hair follicles in the scalp, causing the hair loss. “When the follicles grow again, the shock sometimes changes how they grow, temporarily resulting in a different hair texture and color, which eventually normalizes,” explains Schweiger.

In the article, “Genetic Testing to Predict Hair Loss,” published on HairLoss.com, Dr. Schweiger and Dr. Bernstein discussed the efficacy of genetic tests for hair loss:

[Dr. Schweiger] explains, “I think the test has probably identified a predictor of hair loss but not the only predictor. There is science behind the test and some published research studies; however, the longitudinal, larger studies have not been done, because this testing procedure is just too new.” Dr. Robert Bernstein, M.D., director at Bernstein Medical Center, agrees and adds, “These tests focus on one particular dominant gene, but what is becoming apparent is that hair loss is a complex genetic condition most likely involving several different genes.” He further notes that age, stress, hormone levels, disease and many other factors also are at play in determining factors for hair loss. “Just because a person has the genes for baldness, it doesn’t mean the trait will manifest itself. The truth is the cause and effect have not been proven and differ from person to person, and the association is not anywhere near 100 percent.”

[…]

“Right now, we predict future hair loss based on follicle miniaturization, using advanced microscopic equipment,” says Dr. Schweiger, “and I advise a man to do this at around age 25. If someone presents with more than 25 percent miniaturization, then it’s time to start a hair loss prevention regimen.”

Lastly, Dr. Schweiger contributed featured commentary to an article on HairLoss.com on a topic of importance to those suffering from hair loss, namely, protecting your scalp from the dangerous radiation given off by the sun. In “When You Lose Your Hair, Protect Your Scalp,” Dr. Schweiger encourages bald or balding individuals to take important steps to protect their scalps:

…if you notice your hair thinning or you have baldness of any kind for any reason, it’s important to protect your scalp from sun damage, precancer and skin cancer,” says Dr. Eric Schweiger, M.D., a board-certified dermatologist and hair transplant surgeon at Bernstein Medical — Center for Hair Restoration in New York City. That’s because 100 percent of the surface area on top of your head directly faces the sun’s burning rays when the sun is strongest, between 10 a.m. and 2 p.m. “In general, a mild sunburn on your scalp won’t harm your hair follicles. But any exposure that causes blistering can cause scarring and pre-cancer cells, which will harm hair follicles permanently, so you need to take special care of your scalp when exposed to the sun, even for only a few minutes,” explains Schweiger.

Set up a hair loss consultation with one of our board certified physicians.

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Dr. Christiano Interviewed on Alopecia, Hair Loss by New York TimesDr. Angela Christiano, a colleague of Dr. Bernstein’s at Columbia University, has been studying the causes of alopecia areata and genetic hair loss for many years. She, in fact, suffers from the disease as well.

The New York Times has published a question and answer interview with Dr. Christiano which covers her own struggle with alopecia, her research into the causes of genetic hair loss, and where she sees the field going in the future. Here is one exchange that offers a window into how her research is breaking new ground in the field of hair loss genetics:

Q. When were you able to actually do the study?

A. In 2008. We published our findings this past July. Ours was the first study of alopecia to use a genome-wide approach. By checking the DNA of 1,000 alopecia patients against a control group of 1,000 without it, we identified 139 markers for the disease across the genome.

We also found a big surprise. For years, people thought that alopecia was probably the stepchild of autoimmune skin diseases like psoriasis and vitiligo. The astonishing news is that it shares virtually no genes with those. It’s actually linked to rheumatoid arthritis, diabetes 1 and celiac disease.

Continued discovery by Dr. Christiano and others in the field of hair loss genetics will lead to clues like these, which will shape the future of hair loss treatment. The hope for hair loss sufferers around the world is that a medical treatment can be developed which will effectively cure androgenetic alopecia, or common baldness. There is a lot of ground to be covered and there are many studies yet to be conducted, but progress is being made.

You can read more about Dr. Christiano’s research on our Hair Loss Genetics News page.

Read the article and listen to a two minute audio stream of the interview at the NYT.

Photo c/o Ruth Fremson/The New York Times

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Q: Why do some people have a full head of hair into their seventies or eighties and others start to go bald in their late teens or early twenties? — E.Z., Darien, CT

A: The difference is genetic with the inheritance coming from either side of the family.

Although a person will have the genes his/her whole life, a gene’s expression (also called phenotype) can be quite variable. The factors that cause this variability are still unknown.

Read more about the Genetics of Hair Loss

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Most medical conditions can best be addressed with early diagnosis. Genetic hair loss is no different. A test now has the ability to identify whether or not you may be genetically predisposed to hereditary male pattern baldness (Androgenetic Alopecia).

The HairDX genetic test offers information that can aid you and your doctor in making an informed decision about the treatment of your hair loss.

This test is not a substitute for an examination by a physician experienced in the diagnosis and treatment of hair loss. It offers one more bit of information that, in the context of other data (such as hair loss pattern, scalp miniaturization and family history) can help guide you and your doctor to formulate an appropriate treatment plan.

How does this test work?

This new genetic test examines genetic variables (SNP) which are responsible for recognizing Androgen hormones in our bodies. These specific genetic variants of the X chromosome (the Androgen Receptor or AR gene) are found in 95-98% of bald men.

These genetic differences are associated with Male Pattern Baldness (MPB) and by identifying them; the onset of MPB might be better predicted. If a person is predisposed genetically to these chromosomal variations, they may be more likely to develop male pattern baldness prior to age forty.

The test consists of a simple swab of the inside of your mouth. The skin cells are then sent to the HairDX clinical laboratory for a confidential analysis.

How accurate is the test in predicting baldness?

HairDX tests for a genetic variant of a gene (the androgen receptor gene) found on the X-chromosome that is present in more than 95% of bald men. Sixty percent of patients with this variant experience male pattern baldness before the age of 40. Therefore, if a person has this gene, they would have an increased risk of significant pattern baldness.

Another, less common genetic variant of the same gene (present in about 1 in 6 men) indicates a greater then 85% likelihood that a person will not experience early onset pattern baldness. If a person is found to have this gene, they are unlikely to become very bald.

Why is the genetic test not 100%?

The androgen receptor gene identified thus far is only one of a number of genes that affect hair loss.

How does the test compare to information obtained from a history and physical exam by your physician?

An assessment of scalp miniaturization by an experienced physician using a densitometer, combined with a history and physical, appears to be a far more reliable way of predicting future hair loss. The genetic test can complement this information, but does not replace it.

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Q: What are the genes that cause male pattern baldness?

A: At this time the genes that actually cause hair loss are still unknown. However, there are two gene loci, recently identified, that appear to be associated with common baldness. The first is on the Androgen Receptor (AR) gene carried on the x-chromosome and the second is a non-sex chromosome 20p11.

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It has long been thought that the genes for common baldness come from the mother side of the family – explaining why a male whose maternal grandfather is bald is more likely to lose his hair than if his own father were bald. This observation was recently supported by the discovery of the androgen receptor (AR) gene which resides on the X-chromosome.

Remember, there are two sex chromosomes; X and Y. Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). This means that a male must get his X chromosome from the mother.

But we all have seen that some bald sons have bald fathers, even when no one on the mother’s side of the family has any hair loss. This suggests that the genetics of male pattern alopecia is more complicated, with multiple genes influencing hair growth. And it is likely that the inheritance of baldness is polygenetic, with relevant genes coming from both the x-chromosome of the mother and non-sex chromosomes of either parent. So where are the other genes?

Two independent research groups, one from England and the other Germany, both published in the journal Nature Genetics, have identified a gene locus p11 on chromosome 20 that seems to be correlated with male pattern hair loss, and since the gene is on a non-sex chromosome, it offers an explanation for why the inheritance of common baldness can be from either side of the family. It is important to emphasize that like the AR gene, the chromosome 20p11 locus has only been shown to correlate with hair loss. It is not been shown that either of these genes actually cause baldness.

Unlike many genes whose expression is one or the other (i.e. blue eyes or brown), the 20p11 variations tend to be additive; therefore, men with one affected copy will have a 3.7 fold increase in the chance of having early hair loss and those with two copies a 6.1 fold increase. Men with both the chromosome 20p11 variation and the AR gene will have a seven-fold increase of developing male pattern hair loss at an early age. This gene combination occurs in about 15% of Caucasian men.

The mainstay of predicting future hair loss is with a Densitometer – an instrument used by physicians to measure changes in hair shaft diameter (miniaturization). According to Dr. Robert Bernstein, “Looking at hair shafts under a microscope can spot shrinkage years before it is apparent – we can pick it up when kid are still teenagers.” Early diagnosis is important in androgenetic alopeica because medication is useful only if the hair loss is not too advanced. The genetic studies are significant in that they supply the physician with one more piece of information when developing a master plan for treating a person’s hair loss. See the article in the Wall Street Journal titled, Hair Apparent? New Science on the Genetics of Balding.

While researchers consider these latest discoveries to be of significant merit, caution must be made since these genes are felt to be associated with hair loss, but not yet shown to be causative. More importantly, the associations are not absolute. A clinical evaluation is still the most reliable indicator of future hair loss. Finally, the ability to identify associated genes does not suggest that a “cure” for male pattern baldness is imminent.

Reference
“On the Genetics of Balding,” Wall Street Journal, Vol. 4 – October 1, 2008.

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Jing Gao, Mindy C. DeRouen, Chih-Hsin Chen, Michael Nguyen, et. al.
Genes & Development 22:2111-2124, 2008

The growth of a hair follicle from its developmental cell stage to a hair bearing follicle is through an interactive process between epidermal cells and those of the dermal papilla. It was found that Laminin-511 is instrumental in facilitating this process.

It has been felt that the extra-cellular protein Laminin is critical to both adhesion and the signaling process in hair development; however, the mechanism is not fully understood.

Through this study, it was shown that the signaling pathways introduced by the administration of noggin and sonic hedgehog alone were insufficient to develop a hair follicle. When Laminin-511 protein was introduced to the tissue culture, the dermal papilla developed. When the protein was inhibited, hair follicle growth again ceased. This information supports prior studies suggesting that Laminin is critical in the early stages of follicle cell development and is required for continued follicle development and growth.

This study reaffirms in vitro and in vivo studies in mice, the importance of Laminin-511 in the formation of dermal papilla to promote the development of more organized dermal papilla cells and the hair follicle development. It also suggests that there is a reciprocal mechanism between the signaling pathways of noggin and sonic hedgehog with Laminin-511.

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by Jeff Teumer, PhD
Hair Transplant International Forum, Volume 18, Number 3, May/June 2008

Follicular cell implantation (FCI) is based on the ability of the dermal papilla (DP) cells, found at the bottom of hair follicles, to stimulate new hairs to form. DP cells can be grown and multiplied in a culture so that a very small number of cells can produce enough follicles to cover an entire bald scalp.

In order to produce new follicles, two types of cells must be present. The first is Keratinocytes, the major cell type in the hair follicle, and the second are dermal papillae cells (DP) which lie in the upper part of the dermis, just below the hair follicle. It appears that the DP cells can induce the overlying keratinocytes to form hair follicles. There are a number of proposed techniques for hair regeneration that use combinations of cells that are implanted in the skin. The two major techniques involve either transplanting dermal papillae cells by themselves into the skin or implanting them with keratinocytes. These techniques can be used with or without an associated matrix used to help orient the newly forming follicles.

Implanting Dermal Papillae Cells Alone

  1. Implanting DP cells by themselves into the dermis, with the hope that they will cause the overlying skin cells (keratinocytes) to be transformed from normal skin cells into hair follicles. This method is called “follicular neo-genesis” since new hair is formed where none previously existed.
  2. Cells of the dermal papillae are placed alongside miniaturized follicles. The transplanted cells would induce the keratinocytes of the miniaturized follicles to grow into a terminal hair. A potential advantage of this technique is that the existing miniaturized follicles already have the proper structure and orientation to produce a natural look growth.

Implanting Dermal Papillae with Keratinocytes

  1. A mixed suspension of cultured keratinocytes and DP cells are implanted into the skin.
  2. Keratinocytes and DP cells are cultured together such that full or partial hair formation takes place in a culture dish. These culture-grown hairs, or “proto-hairs,” are then implanted into the patient. The advantage of using a proto-hair is that there would be better control over the direction of hair growth because of the structural orientation of the proto-hair.

Cell Implantation using a Matrix

  1. A variation of the above techniques is to use a matrix to help orient the implanted cells. This could be either an artificial matrix composed of materials such Dacron or it could be a biological matrix composed of collagen or other tissue components. The matrix would act like a scaffold to help cells organize to form a follicle. If the matrix were filamentous (like a hair) it could help direct the growth of the growing follicle. A matrix could be used with dermal papillae cells alone or in combination with cultured keratinocytes.

With all of the varied approaches for FCI, the aim is to combine keratinocytes and DP cells to efficiently and reproducibly generate thousands of follicles for hair restoration. In some cases, cells are combined in vivo and all of the hair formation must take place in the body after implantation, while in others, some hair formation takes place in culture before implantation.

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NY Japion - Dr. Robert M. Bernstein

NY Japion — a weekly newspaper in the Japanese language, published in the New York tri-state area, and distributed for free in the Japanese community — has featured Robert M. Bernstein, MD, in their series on hair loss in men and women. In the series, TV producer, Hideo Nakamura, who is bald himself, goes on a mission on behalf of fellow bald men. His column hopes to help others with hair loss to have a more fulfilled, fun life and to raise their self-esteem.

Nakamura interviewed Dr. Bernstein for this weekly series that began in October 2006. In issues No. 1 and 2, Dr. Bernstein explained the basic mechanism of balding for both men and women which are quite different in its causes, balding types, and progression of hair loss. The NY Japion’s readers were all very surprised by the fact that balding for men is actually related to genes on both the mother’s side as well as the father’s side of the family. Dr. Bernstein also shared his unique theory of why Japan’s Samurai had the uniformed bald look.

The column discussed post-op care after hair restoration surgery and explained the drug Propecia, a men’s oral hair growth treatment, minoxidil and some cosmetic hair products.

Reporter Nakamura was also examined by Dr. Bernstein and with the patient’s permission was allowed to observe a hair transplant surgery. Issues No. 3, 4, 5 are about the surgical hair restoration procedure known as Follicular Unit Hair Transplantation (FUT), a method that Dr. Bernstein helped to pioneer. By using the patient’s own hair, FUT can give totally natural looking results. The patient’s own hair starts growing where there was no hair before.

You can download a PDF version of the original series (in Japanese) at the link below:


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Q: Why do some people have a full head of hair into their seventies or eighties and others start to go bald in their late teens or early twenties?

A: The cause is genetic and this poly-genetic trait can be inherited from the mother’s side, the father’s side, or both.

There is an old wives’ tale that it is inherited only from the mother’s parents. Although the inheritance can come from either side, it is actually greater from the mother’s side – but only slightly.

Read about Hair Loss Genetics

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