A network approach to micronutrient genetics: interactions with lipid metabolism

Although interactions between fat soluble micronutrients and lipid metabolism in relation to absorption, status and body composition have been well described, there is new evidence to suggest that key genes have profound effects on how micronutrients and lipids are handled in a range of cells and organs. This review highlights the importance of genetic variation in folate, selenium, zinc and carotenoid metabolism and the recent findings of micro-macro nutrient interactions.

Although the methylenetetrahydrofolate reductase gene has been linked to CVD for some time, recent findings indicate that single-nucleotide polymorphisms (SNPs) in this gene are also linked to diabetes and may influence the pathogenesis of this disease through elevated alanine amino transferase concentrations. A recent selenium supplementation trial showed that SNPs can affect responses of GPx4, GPx1 and GPx3 protein expression or activity in response to Se supplementation or withdrawal. There is convincing evidence to suggest that the high variability of plasma carotenoids seen in human populations is at least partly caused by multiple genetic variations in genes involved in lipoprotein metabolism and lipid transfer. The most striking evidence of an interaction between carotenoid and lipid metabolism, however, comes from the observation that BCMO1 mice develop liver steatosis independent of the vitamin A content of the diet, and the discovery of common SNPs in this gene indicates that this interaction might be of clinical significance.

Knowledge of genetic variants that affect micronutrient metabolism and responses to micronutrient supplementation were until recently largely limited to methylenetetrahydrofolate reductase. However, identification of novel functional SNPs in BCMO1, the critical enzyme of beta-carotene metabolism, and in several key selenoproteins indicates the potential importance of micronutrient-gene interactions.