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Genetics Not Significant To Developing Typical Parkinson's Disease

Genetic factors do not play a significant role in causing the most common form of Parkinson's disease (PD), according to a study to be published in the January 27, 1999 issue of the Journal of the American Medical Association(1). This epidemiological study, the largest of its kind to investigate the role of genetic or environmental causes of PD, examined 19,842 white male twins enrolled in a large registry of World War II veteran twins.

"This study cuts a wide swath of research opportunities into causes of Parkinson's disease by suggesting that heredity is not a major etiologic component in the largest group of PD patients, those whose disease began after age 50," said Michael D. Walker, M.D., Director of the Division of Stroke, Trauma, and Neurodegenerative Disorders at the National Institute of Neurological Disorders and Stroke (NINDS). The study was funded by the NINDS and The Valley Foundation of Los Gatos, California, a non-profit organization that supports a variety of health care causes, including PD.

For many years, researchers have speculated about the causes of PD, with the primary considerations being genetic determinants and environmental factors. The current study suggests that typical PD -- defined as PD diagnosed after age 50 -- has no genetic component, while the opposite was observed in a small subset (six pairs) of identical and fraternal twins whose PD was diagnosed before age 51 in at least one twin. Investigators concluded that undetermined environmental factors, not genetics, are likely triggers of typical PD and they suggest that research concerning a genetic link to PD be directed toward subjects with earlier onset of the disease.

Twin studies have proven particularly useful in distinguishing the relative contributions of genetics and environment to the cause of various diseases. In the JAMA study, the investigators theorized that if PD had a genetic basis, both individuals in an identical twin pair would be expected to develop the disease (since they have the exact same genetic make-up). Instead, they found that PD most commonly occurred in only one member of a twin pair, whether the pair was identical or fraternal.

"Since purely genetic Parkinson's disease appears to be rare, investigations of genetic forms of parkinsonism, such as in families with multiple-affected generations, will help us to identify the underlying disease mechanisms," said principal investigator Caroline M. Tanner, M.D., Ph.D., of The Parkinson's Institute in Sunnyvale, California, and lead author of the JAMA study.

Study subjects were part of the National Academy of Sciences/National Research Council World War II Veteran Twins Registry, which consisted of 15,924 pairs of white male twins when established in 1959. This study attempted to contact all 19,842 individual twins believed to be alive as of 1992. Pairs were excluded if both twins could not be located, refused to participate, or were known to be dead. If one twin was eligible and the other refused to participate, had dementia, or was dead, a proxy informant was used, either the participating twin brother, a previously provided contact, or a commercially available database.

In brief interviews, all study subjects received screening for suspected parkinsonism, dementia, cerebrovascular disease, eye disease, cancer, and possible risk factors for these diseases. This cohort was ideal for the study, as they had reached an age range of increasing risk for PD. Twins diagnosed in the study as having possible or probable PD were found to exhibit at least two of the four standard symptoms of parkinsonism  tremor, rigidity, postural instability, and bradykinesia (gradual loss of spontaneous movement).

More than half a million Americans have PD, a chronic and progressive motor system disorder that strikes men and women almost equally. The disease usually affects people over age 50, with the average age of onset at 60 years. Up to 50,000 new cases are diagnosed each year. Currently the disease has no cure; standard treatment usually involves the drug levodopa, or L-dopa, but symptoms may return following long-term use of this drug.

NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation's premier supporter of research on the brain and nervous system and a lead agency for the Congressionally designated Decade of the Brain. NINDS celebrates 50 years of brain and nervous system research in the year 2000.

(1) Tanner, C.M.; Ottman, R.; Goldman, S.M.; Ellenberg, J.; Chan, P.; Mayeux, R.; and Langston, J.W. "Parkinson Disease in Twins." Journal of the American Medical Association, January 27, 1999, Vol. 281, No. 4, pp. 341-346.

NIH-National Institute Of Neurological Disorders And Stroke. January 1999.

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