Thirsty Genes Putative Thrifty Genes that May Have Been Selected to Counter Water Stress but Now Lead to Hypertension

Humans have a physiological requirement for salt and mineral sodium. Indeed, one of our most basic senses of taste is for saltiness. This taste is not unpleasant, and it is perhaps unsurprising that in the West, our salt intake far exceeds our physiologic needs. Even the U.S. Food and Drug Administration recommendation of 6 g/day for a low-salt diet is estimated to be 3.5x that of the typical Paleolithic diet. Some people are sensitive to salt and possess a genetic predisposition toward developing life-threatening hypertension (high blood pressure). Ten percent of people are affected by salt sensitivity in this way.

It has been suggested that our early hunter-gatherer ancestors survived on little salt. However, the agricultural revolution and urbanization led to an increase in salt usage with genetically predisposed individuals developing age-related hypertension (64). Lev-Ran and Porta (64) hypothesize that selection pressures may have favored the emergence of a salt-sensitive, hypertensive genotype. This they argue might have been a thrifty gene phenomenon, like the APO-E4 allele mentioned earlier, which supported energy savers in times of scarcity, but in contemporary society contributes to chronic degenerative disease. They suggest that "thirsty" genes may act on salt and water retention and, hence, helped early man survive the challenge of water volume depleting illnesses. This may have been useful under water stress situations, but it is deleterious in respect of causing hypertension in post-reproductive individuals in our aging contemporary societies.

Structural similarity between plant sterols (p-sitosterol) and cholesterol

Intestine Cholesterol Absorption Gene
Figure 2.10. The structural similarity between plant sterols like p -sitosterol and cholesterol results in molecular competition for intestinal absorption. Ancestral diets were rich in plant sterols and, hence, lower in cholesterol and its precursors.

The angiotensin converting enzyme gene ACE I/D (insertion/deletion) polymorphism may be associated with salt-sensitive hypertension and it is certainly a candidate gene for the condition (65), although 20-30% of blood pressure variability is thought to stem from polygenes (66). An interesting hypothesis has been generated that suggests African-Americans may have inherited salt sensitivity from their slave ancestors, because individuals less resistant to salt loss died in transit across the Atlantic Ocean. Those with a genetic predisposition to retaining sodium were at an advantage, however, and survived the arduous sea voyage (67). Although this might explain why, among a hypertensive cohort, 76% of African-Americans were salt sensitive compared with only 56% of Caucasians (64,68), this hypothesis has been criticized on the basis of historical accounts that suggest salt may not have been limiting on these sea voyages (69). The likelihood of this particular hypothesis being correct is impossible to ascertain however; the advent of the agricultural revolution may have added selection pressures that worked on inherited salt sensitivity: Selection for salt sensitivity may have occurred due to the likely decline in hygiene conditions and the spread of diseases as a result of population aggregations associated with urbanization. In this scenario, it is possible that "thirsty" genes acted on sodium and water retention and aided survival from the stress of water volume depleting infectious diseases (64).

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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