Health Problems, Small Genetic Differences

When you get right down to it—and by "right down to it," I mean at the DNA level—we are far more like one another than most of us would care to admit. It is estimated that we are 99 percent genetically identical, with that varying 1 percent causing quite a lot of variance. (The 1 percent explains, for instance, why I'm writing this column instead of sprinting in the Olympics or starring as the next James Bond.) An ever-growing body of research is also demonstrating how some of these differences put us at risk for a variety of diseases, including cancer, Alzheimer’s, and disorders that affect the immune system. Many of these differences are as small as one can imagine: a single change in the order of our DNA.
As I learned in college, and children now learn in elementary school, DNA is made up of four letters, or nucleotides: adenosine (A), guanine (G), cytosine (C), and thymidine (T). At certain points in our genes, we have variations in these letters, called polymorphisms. For example, where one part of the population may have a C, the rest of the population will have a T. These single nucleotide polymorphisms are known in the field as SNPs (pronounced "snips").







In a recent paper in the New England Journal of Medicine, a group of investigators looked at SNPs from over 2,500 patients with two rheumatologic disorders—lupus and rheumatoid arthritis—and compared their DNA with that of over 2,000 normal patients. The scientists concentrated their efforts on 13 different genes on a part of chromosome 2 that had previously been identified as containing genes related to these disorders. Patients with a particular SNP in a gene called STAT4 were 32 percent more likely to have rheumatoid arthritis and 55 percent more likely to have lupus. If you had two copies of this particular SNP (one from each of your parents), then your risk for either disorder was even higher.

Antidepressants

I’m not surprised when a patient tells me she doesn’t want to take antidepressants.They make some people gain weight, and some lose their interest in sex or find it more difficult to have an orgasm. Others just don’t want to take a drug that mucks with their brains. So my interest was piqued by a recent article in The Wall Street Journal that discussed a “backlash against antidepressants sparked by concerns about their safety, efficacy, and side effects [that] is helping drive patients to alternative methods.”

Given what I do for a living (check the byline), my own bias is in the direction of therapies that have been rigorously tested for safety and effectiveness. However, for patients who can’t, won’t, or simply prefer not to go with conventional medicine, a prudent trial of an alternative therapy, like acupuncture or valerian, might be worth considering. But are these alternative approaches truly effective? That’s a tough question, and it depends on what you mean by “effective.”

For a drug to be effective it should work better than a placebo, but in most drug studies the placebo itself often has a measurable success rate—often around 20 percent. Thus, even if an alternative therapy is no more effective than a placebo, you’re still left with a one in five chance of feeling better at the end of the day. For some people, even this 20 percent chance of feeling better is worth it.

Preventing Alzheimer's Disease

More than 5 million Americans have Alzheimer’s disease (AD), and in spite of a worldwide effort to find a cure, our mildly effective therapeutic options remain limited to treatments to slow down the disease. While the search for better treatments goes on, many scientists are looking for treatments to prevent the development of AD.
Therapies that prevent disease, like vaccines, are called primary prevention. Measles, mumps, and rubella are essentially diseases of the past (at least in the United States) because our children are vaccinated at an early age. Unfortunately, a vaccine for AD is still far off.
Recently, some researchers have turned their attention toward primary prevention for AD. That these studies are being conducted at all is exciting, as primary-prevention trials are notoriously difficult to set up and manage. Primary-prevention trials require a large number of people to participate for years at a time. Once you have people in the trial, it’s often a challenge to retain them. Some get bored, others move, and still others have more pressing family obligations. Nevertheless, because of these people, we are beginning to get a better idea of what might and what definitely does not prevent AD.

One trial that started with a lot of hope and ended up with negative results was the Women’s Health Initiative. Prior to the WHI, the accepted view among physicians was that estrogen therapy reduced a woman’s risk of developing cognitive impairment. Unfortunately, the opposite proved to be the case: Women who took estrogen had a slightly higher rate of cognitive impairment than women who didn’t.
On the alternative medicine side, there’s currently a trial of over 5,000 people to see if ginkgo biloba will prevent AD. The study is about halfway done, and in another three years we will be able to see if ginkgo biloba does make a difference or if it is just another example, like estrogen, of hope getting ahead of science.
So, when it comes to primary prevention for AD, we’re not there yet. However, there are lots of good scientists and an even larger number of generous volunteers who are trying to change that. For those who face the daily challenges of having a loved one with this tragic disease and maybe worrying about developing the disease themselves, it is reassuring to know that these primary-prevention trials may lead to effective ways to prevent AD.