Parkinson Disease

What Genes are linked to Parkinson Disease?

 

What Genes are Linked to Parkinson's Disease?

Several genes have now been definitively linked to PD. The first to be identified was alpha-synuclein. In the 1990s, researchers at NIH and other institutions studied the genetic profiles of a large Italian family and three Greek families with familial PD and found that their disease was related to a mutation in this gene. They found a second alpha-synuclein mutation in a German family with PD. These findings prompted studies of the role of alpha-synuclein in PD, which led to the discovery that Lewy bodies from people with the sporadic form of PD contained clumps of alpha-synuclein protein. This discovery revealed a potential link between hereditary and sporadic forms of the disease.

In 2003, researchers studying inherited PD discovered that the disease in one large family was caused by a triplication of the normal alpha-synuclein gene on one copy of chromosome 4.  This triplication caused people in the affected family to produce too much of the normal alpha-synuclein.  This study showed that an excess of the normal form of the protein could result in PD, just as the abnormal form does.

Other genes linked to PD include parkin, DJ-1, PINK1, and LRRK2. Parkin, DJ-1, and PINK-1 cause rare, early-onset forms of PD.  The parkin gene is translated into a protein that normally helps cells break down and recycle proteins.  DJ-1 normally helps regulate gene activity and protect cells from oxidative stress.   PINK1 codes for a protein active in mitochondria. Mutations in this gene appear to increase susceptibility to cellular stress.

LRRK2, which is translated into a protein called dardarin, was originally identified in several English and Basque families and causes a late-onset form of PD.  Subsequent studies have identified this gene in other families with PD as well as in a small percentage of people with apparently sporadic PD. 

Researchers are continuing to investigate the normal functions and interactions of these genes in order to find clues about how PD develops.  They also have identified a number of other genes and chromosome regions that may play a role in PD, but the nature of these links is not yet clear.

Who Gets Parkinson's Disease?

About 50,000 Americans are diagnosed with PD each year, but getting an accurate count of the number of cases may be impossible because many people in the early stages of the disease assume their symptoms are the result of normal aging and do not seek help from a physician. Also, diagnosis is sometimes difficult and uncertain because other conditions may produce symptoms of PD and there is no definitive test for the disease. People with PD may sometimes be told by their doctors that they have other disorders, and people with PD-like diseases may be incorrectly diagnosed as having PD.

PD strikes about 50 percent more men than women, but the reasons for this discrepancy are unclear.  While it occurs in people throughout the world, a number of studies have found a higher incidence in developed countries, possibly because of increased exposure to pesticides or other toxins in those countries.  Other studies have found an increased risk in people who live in rural areas and in those who work in certain professions, although the studies to date are not conclusive and the reasons for the apparent risks are not clear.

One clear risk factor for PD is age.  The average age of onset is 60 years, and the incidence rises significantly with increasing age.  However, about 5 to 10 percent of people with PD have "early-onset" disease that begins before the age of 50.  Early-onset forms of the disease are often inherited, though not always, and some have been linked to specific gene mutations.  People with one or more close relatives who have PD have an increased risk of developing the disease themselves, but the total risk is still just 2 to 5 percent unless the family has a known gene mutation for the disease.  An estimated 15 to 25 percent of people with PD have a known relative with the disease. 

In very rare cases, parkinsonian symptoms may appear in people before the age of 20.  This condition is called juvenile parkinsonism.  It is most commonly seen in Japan but has been found in other countries as well.  It usually begins with dystonia and bradykinesia, and the symptoms often improve with levodopa medication.  Juvenile parkinsonism often runs in families and is sometimes linked to a mutated parkin gene.

National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Brain Resources and Information Network

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