South African blacks, coloureds genetically wired for salt hypertension

A unique gene thought to have originated among the San people has been linked to salt-sensitive hypertension in black and coloured South Africans, making them highly susceptible to strokes and heart disease.

The kidney is an engineering marvel, retaining careful balances of salt and water, and is described as the 'Swiss watch among organs'.

But a genetic abnormality in these groups (and more prominent in black South Africans) means they don't excrete salt as effectively, says specialist nephrologist Professor Brian Rayner, who heads the Division of Nephrology/Hypertension in the Department of Medicine at Groote Schuur Hospital.

"Hypertension in Africa has a different pathophysiology, and the genetics may have to do with Africa's salt-depleted environment," notes Rayner, whose research into the genetics of salt-sensitive hypertension underpinned his recent PhD research. As a clinician scientist, Rayner has been investigating the causes of severe hypertension for the past 15 years.

South Africa has one of the highest rates of hypertension worldwide; 70% of men and 65% of women, according to the Medical Research Council.

"Hypertension is a huge load on hospitals and on the state," says Rayner from his office at GSH.

It's no longer a disease linked to age, weight, or a sedentary lifestyle. Fifty percent of hypertension is based on genetics; therefore, only half on environmental factors.

But the underlying genetics of salt-sensitive hypertension are poorly understood.

Working with a computational bioinformatics team and under the supervision of his colleague Professor Raj Ramesar (Division of Human Genetics), Rayner's task was to search for candidate genes that could be responsible for the variation: those genes with significant variability between the populations.

A novel search engine was developed, and predicted two top candidates: parathyroid hormone precursor (PTH), and AGTR1, a type-1 angiotensin II receptor.

The full sequence analysis of the genes revealed several unique variants not previously described. These will be studied further. Rayner had also worked with Ramesar on another gene candidate, GRK4, an enzyme involved in salt excretion from the kidneys.

"It will be difficult to translate the latest findings into a therapeutic intervention until the underlying genotype is better understood. However, we do know that this gene is linked to response - or lack of response - to certain blood-pressure medication, and it may become a novel site for the development of new antihypertensive drugs."

The rise in hypertension over the past 10 years has also changed referral patterns at the hospital's renal clinic. "Now we're seeing many people under the age of 30 with hypertension," notes Rayner.

They're also seeing many patients with uncontrolled blood pressure as a result of hypertension, despite medication. And salt itself works to counteract the effects of hypertension medication.

Diet is a major concern.

"Up to 70% of our salt intake is through food," notes Rayner. "A reduction of only 10% in the average South African will have an impact on hypertension."

He is fully behind the Department of Health's proposed legislation to lower the salt content in foods (bread is a leading culprit, followed by margarine, butter and cereals). But this should be coupled to public education about the dangers of salt-laden processed and fast foods, and the use of discretionary salt (the salt you sprinkle on your breakfast eggs).

In the background is another threat: HIV and hypertension. While people on ARVs are living longer, the two epidemics are on a collision course. "There is great concern that HIV and hypertension will interact to increase the risk of complications," adds Rayner.

"Our initial research shows that subjects with HIV infection have lost their circadian rhythm in relation to BP, and this is not restored by treatment with ARVs. This suggests that people living with HIV are at increased risk of cardio-vascular disease."

Story by Helen Swingler. Image by Micheal Hammond.