Study Seeks to Determine Why One Sibling Gets Sick, and the Other Doesn't

Episode # 43
Uploaded: July 23, 2010
Running Time: 7:13

SCHMALFELDT:From the National Institutes of Health in Bethesda, Maryland, this is CLINICAL CENTER RADIO.

For decades, scientists have investigated the environment's influence on the development and progression of human disease. For example, what are the factors that cause one sibling to come down with a disease while the other sibling doesn't? A clinical trial conducted at the NIH Clinical Center by the National Institute of Environmental Health Sciences is investigating this question within the families of patients with systemic autoimmune diseases. Dr. Frederick W. Miller, principal investigator in the Environmental Autoimmunity Group at the NIEHS explains.

MILLER: The NIEHS twin sib study is an attempt to begin to understand why some patients develop a disease while their brothers or sisters do not… we do think that most diseases actually are the result of the interactions of genetic and environmental factors and this is true also for the autoimmune diseases that we are studying, which include in this particular study rheumatoid arthritis, lupus, scleroderma, and an autoimmune disease that affects muscle called myositis. And we are studying this both in adults and children.

SCHMALFELDT: This study is comparing adults and children diagnosed with the conditions Dr. Miller listed compared to their same sex siblings who are within four years of age. The siblings must also have the same parents and the affected twin or sibling must have been diagnosed within the past four years. The similarity in the genes of the siblings will help the researchers identify the environmental factors that cause one person to get sick and the other to remain healthy.

RIDER: There is a lot we can learn from being able to study both kids and adults together. We are able to learn what's shared among kids and adults that have very similar conditions and we are also able to see some of the differences between kids and adults that certainly in environmental exposures. We think that kids may have different exposures than adults or they may even react to the same environmental exposure in a different way, and this is becoming clear from other diseases and other environmental exposures.

SCHMALFELDT: That was Dr. Lisa Rider, deputy chief of the Environmental Autoimmunity Group. She talked about the kinds of environmental factors the team is investigating that might influence disease development.

RIDER: I just want to expand a little on Dr. Miller's point of what environmental things that we're studying. Dr. Miller mentioned infections and non infectious exposures. Some of the things that we want to investigate include things like vaccines, they include smoking in the home or by the person, stressful life events, pregnancy issues. Even going back if you have a child who has never been pregnant, even the mother's pregnancy with that child - there might be something even prior to birth or at birth that's going on, and we have some evidence for that with some of our other studies. Sun exposure, work and hobby exposures, medications, dietary supplements, those are some of the things that we're looking at through the questionnaires.

SCHMALFELDT: Dr. Miller said this study has already borne fruit, so to speak.

MILLER: We have actually already published one paper from this study, from the initial analysis of the identical twins and found that in looking at rheumatoid arthritis, lupus and myositis identical twins for what's called epigenetics, which are changes in the DNA structure that occurs as a result of environmental exposures, that it was only the lupus patients actually that showed these changes and not the rheumatoid arthritis or myositis patients. And there were actually many dozens of genes that underwent these methylation changes, these epigenetic changes in the affected individuals compared to the unaffected identical twin in the lupus pairs. And these mostly related again to these immune response genes, that are important in regulating how the body deals with various environmental exposures. I think this is a very interesting finding and has implications beyond this study and beyond this disease as well.

SCHMALFELDT: In addition to the Clinical Center, this study is being conducted at the NIEHS clinical research unit in North Carolina, and in your own home town. Patients can also enroll through their own doctor's offices provided their physicians are willing to help with the research project. The NIEHS research team hopes to not only learn about environmental or genetic factors that influence the development of autoimmune diseases, but also to use that information to prevent disease development in the future.

MILLER: Right now our whole model of medicine is based on the either curative or treatment approach to medicine. It is sort of all after the fact and we really want to change that and change our whole approach to health care, by actually making this a preventative situation where we can actually potentially tell people in advance based on their genetics what are the environmental risk factors that they should avoid to develop disease. We are hopeful that at some point in the future we will be able to make those connections and prevent the development of some of these diseases.

SCHMALFELDT: If you would like more information about this study or one of the 1,500 other studies offered at the NIH Clinical Center, log on to http://clinicalcenter.nih.gov, or e-mail prpl@mail.cc.nih.gov. You may also call our call center toll free at 1-866-999-5553. From America's Clinical Research Hospital, this has been CLINICAL CENTER RADIO. In Bethesda, Maryland, I'm Bill Schmalfeldt at the National Institutes of Health, an agency of the United States Department of Health and Human Services.

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