Tracking a genetic basis for alcohol-related hypertension

Hypertension (high blood pressure) leads to strokes, cardiovascular disease, and kidney
disease.
Chronic alcohol consumption is a major risk factor for hypertension.
The human and mouse genomes share a high similarity in their makeup.
A study has found that one strain of mice has a very different blood pressure response to acute alcohol exposure than other strains did.
A person's genetic background may influence their blood-pressure response to alcohol.

Hypertension (high blood pressure) is one of the leading risk factors for strokes, cardiovascular disease, and kidney disease. Chronic alcohol consumption is a major risk factor for hypertension. A study in the October issue of Alcoholism: Clinical & Experimental Research examines three seldom-linked areas of research - blood pressure, alcohol, and genetics - to determine if genetics may influence blood pressure response to alcohol.

Nearly 50 million Americans age six and older have hypertension, according to the American Heart Association. In 1997, hypertension was listed on death certificates as the primary cause of death for 42,565 Americans (2.13%), and the primary or contributing cause of death for approximately 210,000 Americans (10.5%), out of the more than 2,000,000 who died that year. In general, blacks have a higher prevalence than whites, and men have a higher prevalence than women do. The exact causes of 90 to 95 percent of hypertension cases remain unknown, but alcohol consumption is one of the most important lifestyle factors that can contribute to an increase in blood pressure.

"Having two drinks per day or less, on average," said Daniel C. Hatton, associate professor of behavioral neuroscience at Oregon Health Sciences University and lead author of the study, "appears to have a positive effect on cardiovascular health. Beyond that, blood pressure increases and the risk of cardiovascular disease increases as well. We were interested in knowing whether genetic background could influence blood pressure response to alcohol in a mouse model that allowed controlled blood alcohol levels."

Human and mouse genomes have about an 80 percent similarity in the way genes are organized on chromosomes, a phenomenon known as linkage homology. Hatton and his co-researchers studied mice with different genetic backgrounds - five inbred strains - to see if they would respond to alcohol in different ways. All of the mice within a given strain are identical. In addition, the blood-pressure response of mice to alcohol is very similar to that of humans. The study's findings, therefore, are an approximation of what would happen if researchers were able to do the same study in humans that shared the same genotype, such as five different groups of identical twins.

"We found that one of the strains was very different from the other strains," noted Hatton, "because the animals had an increase in blood pressure in response to acute alcohol exposure rather than a decrease as the other strains did. This finding suggests that some genotypes may be predisposed to having greater increases in blood pressure with alcohol consumption and therefore greater risk of hypertension."

"When one considers the findings of this study," said Abdel A. Abdel-Rahman, Distinguished Research Professor of pharmacology at The Brody Medical School, "it becomes apparent that different individuals will respond differently to a given amount of alcohol. Yet we need to remember that these experimental studies are conducted under controlled conditions. In real life, there are other factors that - along with the genetic predisposition - may influence blood-pressure response to ethanol."

One group that concerns Abdel-Rahman includes those being treated for hypertension while continuing to drink. "While alcohol attenuates the hypotensive action of some medications," he said, "it accentuates the action of others. Either of these interactions is expected to lead to inadequate control of blood pressure in hypertensive individuals who continue to consume alcohol along with the therapy intended to treat hypertension."

Yet Abdel-Rahman is clearly enthusiastic about the discovery of a potential impact of genetic traits on blood-pressure response to alcohol. He said the study's findings 'set the stage' for more detailed future work in an exciting area of research. "These results pertain to the acute effects of alcohol on blood pressure," he said. "It remains to be determined if the long-term effects of alcohol on blood pressure are influenced by genetic traits, and if so, whether the same or different genes influence the acute and the chronic blood pressure responses to alcohol."

This is, in fact, the direction that Hatton proposes to follow. "We have plans to chronically expose selected strains of mice to alcohol," he said. "Following this, we will begin gene mapping studies to identify the exact genes responsible for the rodents' sustained elevations in blood pressure."

Co-authors of the Alcoholism: Clinical & Experimental Research paper included:
Yue Qi of the Department of Behavioral Neuroscience at Oregon Health Science University
J.K. Belknap of the Department of Behavioral Neuroscience at Oregon Health Science University, and Veterans Affairs Medical Center, Portland.
The study was funded by the National Institutes of Health, and the Department of Veterans Affairs.

Contact: Daniel C. Hatton, Ph.D.
hattond@ohsu.edu
503-494-2013
Oregon Health Sciences University

Add'l Contact: Abdel A. Abdel-Rahman Ph.D.
abdelrahmana@mail.ecu.edu
252-816-3470
The Brody Medical School

Message posted by: Wouter Kalle