Apolipoprotein A-IV polymorphisms and diet-gene interactions.

Abstract

Apolipoprotein A-IV is a 46kDa glycoprotein that is synthesized by intestinal enterocytes and is incorporated into the surface of nascent chylomicrons. Considerable evidence suggests that apolipoprotein A-IV plays a role in intestinal lipid absorption and chylomicron assembly. We have proposed that polymorphisms that alter the interfacial behavior of apolipoprotein A-IV may modulate the physical properties and metabolic fate of plasma chylomicrons. Of the reported genetic polymorphisms of apolipoprotein A-IV, two, Q360H and T347S, are known to occur at high frequencies among the world populations. Biophysical studies have established that the Q360H isoprotein displays higher lipid affinity; conversely the T347S isoprotein is predicted to be less lipid avid. Recent studies have shown that the Q360H polymorphism is associated with increased postprandial hypertriglyceridemia, a reduced low-density lipoprotein response to dietary cholesterol in the setting of a moderate fat intake, an increased high-density lipoprotein response to changes in total dietary fat content, and lower body mass and adiposity; the T347S polymorphism appears to confer the opposite effects. Studies on the diet-gene interactions of other apolipoprotein A-IV alleles are needed, as are studies on the interactions between apolipoprotein A-IV alleles and other apolipoprotein polymorphisms.