Genetic polymorphisms in methyl-group metabolism and epigenetics: Lessons from humans and mouse models

作者：Zeisel Steven H^*

来源：Brain Research, 2008, 1237: 5-11.

DOI：10.1016/j.brainres.2008.08.059

• Choline
• Brain development
• Single nucleotide polymorphism
• Dietary requirement

Choline is an essential nutrient that is critical during fetal brain development. Choline deficiency, through disturbing methyl metabolism, may alter DNA methylation and thereby influence neural precursor cell proliferation and apoptosis. This results in long term alterations in brain structure and function, specifically memory function. A recommended dietary intake for choline in humans was set in 1998, and a portion of the choline requirement can be met via endogenous de novo synthesis of phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT) in the liver. Though many foods contain choline, many humans do not get enough in their diets. When deprived of dietary choline, most adult men and postmenopausal women developed signs of organ dysfatty liver, liver or muscle cell damage). However, only a portion of premenopausal women developed such problems. The difference in requirement occurs because estrogen induces expression of the PEMT gene and allows premenopausal women to make more of their needed choline endogenously. In addition, there is significant variation in the dietary requirement for choline that can be explained by common genetic variants (single nucleotide polymorphisms; SNPs) in genes of choline and folate metabolism. Some of these increase the risk of choline deficiency many fold. These variations in choline requirement could have important implications for brain development.

• 出版日期2008-10-27