Mayo Clinic in Rochester

Wednesday, March 19, 2003

Mayo Clinic Researchers Identify Differing Risk Factors Contributing
to Parkinson’s Disease in Men and Women

ROCHESTER, Minn. -- New Mayo Clinic research provides evidence that
environmental factors may play a greater role in the development of
Parkinson’s disease in men, while for women, hereditary factors may
play a greater role. The findings, to be published in the journal
Movement Disorders, will be available Wednesday for early viewing
online at http:/ /www.interscience.wiley.com/jpages/0885-3185/.

The investigators performed an innovative two-step statistical
analysis to study Parkinson’s disease risk factors. They found that
complex interactions between common gene variants contribute to
Parkinson’s disease risk in women. The researchers postulate that
environmental exposures often are sufficient to lead to Parkinson’s
disease risk in men.

"For women, genetic predisposition may be more important because they
are less exposed to environmental risk factors linked to Parkinson’s
disease in previous research. Also, estrogen may protect women’s
brains from the effects of these environmental factors," says
Demetrius Maraganore, M.D., Mayo Clinic neurologist and one of the
study authors.

The medical community has known for many years that the incidence of
Parkinson’s disease is lower in women than in men, but the exact
reasons have remained a mystery. Now, Dr. Maraganore and colleagues
at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., have
proposed an explanation.

"The causes of Parkinson’s disease differ between men and women,"
says Dr. Maraganore. "Traditionally, men have been out in the
workforce becoming exposed to environmental risk factors such as
pesticides and industrial chemicals or suffering head injuries. By
contrast, women have been less exposed to these factors and require a
stronger genetic susceptibility to develop Parkinson’s. Furthermore,
estrogen, the main sex hormone in women, reduces the risk of
developing the disease.

"For a woman to get Parkinson’s disease, she has to inherit certain
gene variants," says Dr. Maraganore. Hormonal factors combined with
more limited environmental exposure may help protect women from
Parkinson’s disease.

In this study, Mayo Clinic researchers discovered an interaction
between common variants of two genes -- ubiquitin carboxy-terminal
hydrolase L1 (UCHL1) and a-synuclein -- that leads to a significantly
higher risk of Parkinson’s disease than commonly occurs in the
population. Rare mutations in these two genes as well as in a gene
called "parkin" also have been shown to cause rare inherited forms of
Parkinson’s disease.

The Mayo Clinic researchers performed genetic tests on blood samples
from 319 unrelated Parkinson’s disease cases and 196 cases with no
evidence of Parkinson’s disease. These patients are all part of
ongoing Mayo Clinic studies of the causes of Parkinson’s disease led
by Dr. Maraganore and his colleague, Walter Rocca, M.D., Mayo Clinic
epidemiologist.

Following the genetic studies, the researchers conducted a unique
statistical analysis. Step one involved an automated search
(recursive partitioning) for possible genetic interactions from the
data collected about the study participants’ DNA. Following this
search, the investigators conducted a test of the significance of the
gene interactions discovered.

The Mayo Clinic researchers currently are conducting further studies
to test their hypothesis that environmental factors play a greater
role in Parkinson’s in men, while genetic factors play a larger role
in women.

Parkinson’s disease is a progressive condition that causes a movement
disorder including generalized slowness, tremulousness and
immobility. It may develop when motor-control circuits deep in the
brain become disordered as a result of selective-cell degeneration.

The National Institute of Environmental Health Sciences, the National
Institute of Neurological Disorders and Stroke, and Mayo Foundation
funded this study.

Lisa Copeland
507-284-5005 (days)
507-284-2511(evenings)
email: [log in to unmask]

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Reference: http://www.interscience.wiley.com/jpages/0885-3185/

SOURCE: Mayo Clinic
http://www.mayoclinic.org/news2003-rst/1693.html

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