Study
looks for genetic predictors of hypertension
by Toni Baker
Whether genes responsible for a rare disorder that dramatically elevates blood pressure predict hypertension is the focus of a new study.
The disorder is Liddle syndrome, first reported in 1963 in a 15-year-old Alabama girl diagnosed with a blood pressure of 180/110 mmHg, said Dr. Yanbin Dong, molecular geneticist and cardiologist at MCG.
Interestingly, an inexpensive diuretic worked best to manage her problem. Years later, tests found that genes involved in the channel that recycles sodium from food into her body were drastically mutated. “This mutation enables sodium to come back into the body like a flood,” said Dr. Dong.
Today, he is studying sodium channel genes implicated in Liddle syndrome to identify less severe 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.
Dr. Dong is exploring findings by Dr. Gregory A. Harshfield, director of the Georgia Prevention Institute, that some healthy youths, particularly blacks, continue to retain sodium after stress. This occurs in about 36 percent of healthy black youths and 25 percent of healthy white youths, according to Dr. Harshfield’s studies.
The body naturally increases blood pressure during stress, immediately by constricting blood vessels and longer term by directing the kidneys to retain sodium to increase blood volume, said Dr. Harshfield, a co-investigator 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.
He is recruiting 300 healthy blacks age 15 to 19 with normal blood pressure to a Georgia Prevention Institute study that first measures sodium-handling following environmental stress, then analyzes the genes of those who don’t handle it well.
Study participants will be on a salt-restricted 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, SGK-1 and Nedd4-2 – taken from blood samples will be analyzed so specific variations can be correlated with variations in a youth’s ability to excrete sodium after stress. Gene-to-gene interactions also will be studied.
Researchers say poor sodium-handling is a major player in hypertension and that a youth’s reduced ability to excrete salt following stress predicts future health problems. If Dr. Dong’s hypothesis holds, young people with risky genetic variations could have advance warning of their increased hypertension risk and make changes such as salt intake restriction and stress reduction management to avoid the problem.
Other co-investigators are Dr. Haidong Zhu, molecular geneticist; Dr. Harold Snieder, genetic epidemiologist; and Dr. David Ludwig, biostatistician.