Environment influences genetic diseases

May 1, 2005

New Orleans — When it comes to studying genetic diseases of the skin, the popular mantra that "It's all in the DNA" doesn't tell the whole story.

When people think of dermatology and genetics, says Lowell Goldsmith, M.D., "One of the ideas that we've been sold by the popular media, Time magazine and the professional geneticists is that genetics is everything. However, environment plays a tremendous role in genetic diseases, both in the simple Mendelian (dominance versus recessive) diseases and our more common diseases in dermatology, such as psoriasis, atopic dermatitis (AD) and cancers." says Dr. Goldsmith, professor of dermatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, N.C.

Examples of influence A prime example of his point comes from Charles Darwin's discovery of the Galápagos Islands finches, whose beaks were shaped over time by the food available on individual islands.

Dr. Goldsmith witnessed a similar example early in his career while studying a family afflicted by blistering of the palms and soles with severe corneal involvement.

"I found out that this was due to an abnormality of tyrosine metabolism. That is, tyrosine, which comes from the amino acids of proteins in the diet, actually caused inflammation of the skin. And I was able to control this disease by controlling the amount of tyrosine in the diet with a diet very similar to the one used in phenylketonuria (PKU)," he says.

Along with PKU and tyrosinemia, simple genetic diseases wherein environment plays a role include dermatitis herpetiformis, a disease impacted by wheat gluten.

"We have a variety of diseases in the skin in which sunlight is a factor in the presence of a certain genetic trait," Dr. Goldsmith adds.

Examples include the various porphyrias, xeroderma pigmentosum and Bloom syndrome. Ectodermal dysplasias, on the other hand, flare up in response to environmental stimuli such as temperature. Similarly, moisture exerts impact upon Hailey-Hailey disease.

Genetics only a part In studying such disorders, he says, "Genetics alone aren't going to tell us enough. Understanding that the environment is a very important factor means that we have ways of controlling these diseases in addition to or even before we're able to do specific genetic manipulations in these diseases."

Environments, furthermore, need not be as big as islands. For example, Dr. Goldsmith believes nighttime itching suffered by patients with AD or atopic eczema occurs because patients open up the "private environment" next to their skin when undressing for bed.

"One of the ways we know this environment exists is that when you're behind someone who's wearing perfume, you're able to get the scent of the perfume," he says. "This same technique is being used to detect people who have been exposed to explosives, in that they actually carry some of the explosive material in a plume which can be picked up by sensitive detection."

Dr. Goldsmith's emphasis on environment may ruffle feathers, but he believes it's a concept whose time has come.

"I'm talking about the etiologies of etiologies - the causes of cause. I take a model from epidemiology, where we're concerned about the host, the environment and vectors. We must expand our concept of disease because this gives us whole new ways of treating disease," he says.

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