Study Seeks Genetic Predictors of Hypertension

MCG researchers are studying the rare disorder, Liddle syndrome, in search of genetic risk factors for hypertension.

The disease was first reported in 1963 in a teen with high blood pressure. Interestingly, an inexpensive diuretic worked best to manage her problem. Tests years later found the reason was that genes involved in the channel that recycles sodium from food into the body were drastically mutated. “This mutation enables sodium to come back into the body like a flood,” said Dr. Yanbin Dong, an MCG molecular geneticist and cardiologist.

He is looking at sodium channel genes implicated in Liddle syndrome to identify subtler changes that could be used to screen for hypertension risk in the general population.

“My hypothesis is if Liddle syndrome is caused by these nasty, drastic mutations, maybe the majority of hypertension can be caused by milder, less nasty polymorphisms or variations in the same genes,” said Dr. Dong, who received a $1.43 million grant from the National Heart, Lung and Blood Institute to test his theory.

He is recruiting 300 healthy black teens with normal blood pressure for a Georgia Prevention Institute study that first measures sodiumhandling following environmental stress, then analyzes the genes of those who don’t handle it well.

Dr. Dong is exploring findings by Dr. Gregory A. Harshfield, director of the Georgia Prevention Institute, that some healthy youths continue to retain sodium following stress. He documented this impaired stressinduced pressure natriuresis in about 36 percent of healthy black youths and 25 percent of healthy white youths.

Blood pressure naturally rises during stress, immediately by constricting blood vessels and longerterm by directing the kidneys to retain more sodium and so increase blood volume, said Dr. Harshfield, a coinvestigator on Dr. Dong’s latest grant. His own studies have shown the importance of the interaction between salt and stress in regulating blood pressure.

The new study should provide additional insight into the relationship between salt and stress as well as diet and genetics, Dr. Dong said.

Study participants will be on a saltrestricted diet for four days, then come to the GPI on the fifth day to rest for an hour, play competitive video games and rest again. Blood pressure and sodium excretion will be measured before games are played, immediately afterward, then two hours later.

The five genes—alphaENaC, betaENaC, gamma ENaC, SGK1 and Nedd42—will be analyzed from blood samples so specific variations can be correlated with the ability to excrete sodium following stress. Genetogene interactions also will be studied.

If Dr. Dong’s hypothesis holds, young people with genetic risks for hypertension could have advance warning and make changes—such as a lowsodium diet and stress management—to ideally avoid the problem.

Toni Baker