Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline

Abstract

SummaryRecent progress in the understanding of the human dietary requirement for choline highlights the importance of genetic variation and epigenetics in human nutrient requirements. Choline is a major dietary source of methyl-groups (one of choline's metabolites, betaine, participates in the methylation of homocysteine to form methionine); also choline is needed for the biosynthesis of cell membranes, bioactive phospholipids and the neurotransmitter acetylcholine. 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 dysfunction (fatty liver, liver or muscle cell damage, and reduces the capacity to handle a methionine load, resulting in elevated homocysteine). 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 polymorphisms in genes of choline and folate metabolism. Choline is critical during fetal development, when it alters DNA methylation and thereby influences neural precursor cell proliferation and apoptosis. This results in long term alterations in brain structure and function, specifically memory function. IUBMB Life, 59: 380-387, 2007

Randomized, double-blind, placebo-controlled clinical trial of choline supplementation in school-aged children with fetal alcohol spectrum disorders

“…Furthermore, caregivers were asked to refrain from administering any cognitiveenhancing medications on testing days; however, this may not have been sufficient given the cumulative effects of these medications and depending on their half-life or washout time. Finally, single nucleotide polymorphisms can influence metabolic efficiency and, consequently, an individual's dependency on dietary choline (59)(60)(61), which may underlie interindividual variability in responsiveness to supplementation. Despite these limitations, the current study had many notable strengths and adds to the available literature in several respects.…”

Choline in acute coronary syndrome: an emerging biomarker with implications for the integrated assessment of plaque vulnerability

“…Studies indicate a weak inverse relationship between PCho and the time since the last meal [30], and they demonstrate that the human requirement for choline is influenced by genetic factors [50]. Higher intakes of choline and betaine are not protective for incident coronary artery disease [51].…”

“…The reasons for these discrepancies in study results may be attributed to differences in patient populations. The studies of Danne et al 2003 and2007 also included patients with other signs suggesting acute cardiac ischemia, including acute cardiopulmonary arrest probably due to acute myocardial ischemia [9,53]. Such patients have a high likelihood of elevated choline levels due to severe global ischemia and also high rates of subsequent MACE such as cardiac death and left ventricular (LV)-failure.…”

Epigenetics: Impacts on Disease Susceptibility and Pharmacotherapy

“…The pathways include the formation of betaine, methionine from homocysteine, and other choline metabolites. 9,20 Besides this, choline is also important in the biosynthesis of acetylcholine, bioactive phospholipids, and cell membranes. In general, dietary choline is very essential, although the major portion of dietary choline is produced via endogenous denovo synthesis.…”

“…9,20 The choline usually donates methyl groups during the production of the various metabolites. The pathways include the formation of betaine, methionine from homocysteine, and other choline metabolites.…”