In a study, published in the American Journal of Hypertension, researchers at the University of Michigan ( U-M ) have reported that blood pressure was higher, and more likely to rise with age, among people who had an extra-long form of a gene called DRD4.

They made the discovery by studying the genes of 864 people from 286 families taking part in a long-term blood pressure genetics study called GenNet.

The families all live in or near the town of Tecumseh, Michigan, which since 1958 has been home to a U-M clinical research initiative called the Tecumseh Community Health Study.

The finding of a link between DRD4 and blood pressure came as a surprise to researchers who tested this gene initially to look at genetics and behavior.

Cells use the DRD4 gene to make a receptor for a chemical called dopamine, which transmits messages between cells. Dopamine is best known for its role in the brain, where it is involved in feelings of pleasure, and in governing movement. Some studies have suggested that variations in genes for dopamine receptors are linked to certain behavioral traits or personality types

. But in recent years dopamine has also been found to play a role in regulating the release of salt by the kidneys. The new U-M finding adds more evidence for that role.

" While many genes are involved in blood pressure and the inherited risk of developing hypertension, we're learning that variations in genes for dopamine receptors play a significant role," says senior author Alan Weder, at the U-M Medical School. " As we learn more, we may be able to determine which patients need the most aggressive blood pressure treatment, and to develop drugs that can lower blood pressure by intervening directly in the proximal tubules of the kidneys, where dopamine acts -- something today's drugs don't do."

The new study is the first to show that the DRD4 receptor plays a role in the regulation of blood pressure by the kidneys, and to show that a common variation in the gene is associated with higher blood pressure. Two other dopamine receptors have previously been shown to be linked to blood pressure regulation.

One in four American adults has hypertension. If high blood pressure isn't lowered with the help of diet, exercise and medication, it can dramatically raise the risk of heart attack, stroke or kidney problems.
Blood pressure, especially the systolic pressure, tends to rise as a person gets older. And in older people, high systolic pressure is considered the greatest risk factor for cardiovascular disease.

" This gene variation may be useful in developing a predictor of which patients are likely to have a rapid rise in blood pressure as they age, and may need more aggressive monitoring and treatment," Weder says. However, he and his co-authors say, no one gene variation is enough to predict an individual person's blood pressure tendencies, and further research on the genes involved in hypertension will be needed.

The other important implication of the finding is to create a fuller understanding of dopamine's action in the kidneys, and changes in that action brought about by variations in the receptor gene. Dopamine in the kidney helps the body respond to large loads of sodium, or salt, coming into the body. After a salty meal, for example, higher levels of dopamine can be detected in the urine after being produced and used by the kidneys to regulate the removal of salt from the body.

Problems or perturbations anywhere in the system that produces dopamine or receives its signals on the cell surface could alter someone's ability to regulate sodium levels, and therefore blood pressure, Weder explains.

Source: University of Michigan Health System, 2005


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