Scientists have determined that the body's overall response to salt is genetically determined, and there is overwhelming evidence that multiple genes are involved.
While the cause of most hypertension is unknown, and less than one-fifth of the 500 million affected people have their pressures adequately controlled through treatment, dietary salt intake is known to be one of the most important environmental determinants of human hypertension. In as many as one third of hypertensive patients, known as "salt-sensitive hypertensives," blood pressure is associated with dietary salt content.
To date, only genes causing rare forms of salt-sensitive hypertension have been detected and do not account for the vast majority of cases of salt-sensitive hypertension.
Studies over the years have shown that people have evolved and can remain healthy on sodium intakes of 200 mg or even less. But with the advent of fast foods, convenience foods and processed foods, there has been an increasing trend in the amount of salt consumed in a person's daily diet.
The average consumption of sodium today amounts to about 8-15 g of salt (sodium chloride). The consequence of this trend is that more of the public is resorting to low-salt diets, assuming that such a course of action will result in lower blood pressure. This may not bring about expected results.
There is great inter-individual variability of blood pressure in the response to salt with some individuals experiencing no increase on a high salt diet while others have a significant increase on a moderate salt diet. Determining which patients will benefit from a low salt diet is a primary goal that will assist in identifying an optimum treatment regimen for those suffering from hypertension.
A new research effort has used a global gene screening tool, DNA microarrays, and salt-sensitive and salt-resistant rat strains to identify genes associated with salt-sensitivity. The principal investigator of the study was Dr Robert S. Danziger, University of Illinois, Department of Medicine, Division of Cardiology, West Side VA, who presented the findings at the Experimental Biology meeting in New Orleans, US, last week.
A powerful new approach, transcriptional profiling using DNA microarrays, was used to probe the genetics of hypertension in general and salt-sensitivity in particular. This is the same methodology that is being used to study other complex diseases such as cancer and schizophrenia. This approach permits the expression of thousands of genes in a tissue or cell to be simultaneously analysed.
The study used a comparison of transcriptional profiles of kidney from two strains of rat, salt-resistant normotensive and salt-sensitive hypertensive, on high and low salt diets. To discover genes that cause salt-sensitive hypertension, identification of gene clusters unique to salt-sensitive rat strains was performed.
A total of 32 genes were identified that are regulated by dietary salt through the transfer of genetic code information. Of these, 10 novel genes were determined to be particularly good new candidates for salt-sensitive hypertension since they had differential transcriptional regulation in salt-resistant normotensive versus salt-sensitive hypertensive rats strains.
The research used DNA microarrays to identify novel genes involved in the physiological adaptation to dietary salt, a known factor in human hypertension.
By comparing transcriptional profiles of kidneys from salt-sensitive and salt-resistant strains of rat, at least 10 new candidates for salt-sensitive hypertension have been identified. These include a number of genes previously not known to be involved in salt handling or blood pressure.
The authors stressed that the findings do not suggest that patients with hypertension should assume that their genetic composition would allow increased sodium intake. The results may however lead to the identification of the major genes associated with salt-resistance and salt-sensitive hypertension.
Therefore, this work may determine new therapeutic approaches to based on genetics and new targets for common forms of hypertension in humans.