CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

BACKGROUND: Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989–1991. RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38–0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97–3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. CONCLUSION: Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved

Review: Nutritional support for patients with cirrhosis

Nutritional support is indicated when cirrhotic patients undergo surgery because they are malnourished, hypercatabolic and immunocompromised. However, the choice of nutrient may be problematic as the liver itself is the central organ of protein, fat and glucose metabolism. Branched chain amino acid- enriched solution may be the choice of protein source, as it is anticatabolic and it stimulates liver regeneration. Excessive glucose is undesirable as it may suppress endogenous fat utilization, which may be the preferred pathway of metabolism after hepatectomy. Medium chain triglycerides are preferred to long chain triglycerides as they are readily utilized and are not deposited in the liver; however, the tendency of cirrhotic patients to accumulate free fatty acids and glycerol after infusion of triglycerides dictates their use intermittently. Clinical studies have shown that perioperative nutritional support is beneficial in cirrhotic patients undergoing major hepatectomy or liver transplantation. The judicious choice of nutrient, care of the catheter and a limitation of the fluid infused are all prerequisites for the efficient use of perioperative nutritional support, which is complementary to a technically perfect operation.link_to_subscribed_fulltex

Nested Case-Control Study of One-Carbon Metabolites in Mid-Pregnancy and Risks of Cleft Lip With and Without Cleft Palate

Evidence exists for an association between use of vitamin supplements with folic acid in early pregnancy and reduced risk for offspring with cleft lip with/without cleft palate (CLP). A few observations have been made about nutrients related to one-carbon metabolism other than folate. Our prospective study attempted to extend information on nutrition and CLP by measuring nutrient analytes in mid-pregnancy sera. This study included data from a repository of women’s mid-pregnancy serum specimens collected in California from 2003–04. Each woman’s specimen was linked with delivery information to determine whether her fetus had CLP or another structural malformation, or was nonmalformed. We identified 89 CLP cases. We randomly selected 409 specimens as controls. Specimens were tested for homocysteine, methylmalonic acid, folate, vitamin B(12), pyridoxal phosphate, pyridoxal, pyridoxic acid, riboflavin, choline, betaine, methionine, methionine sulfoxide, cysteine, cystathionine, arginine, and asymmetric and symmetric dimethylarginine. We observed three analytes with odds ratios unlikely to be explained by random variation, i.e., elevated CLP risks were observed for low levels and for high levels of pyridoxal phosphate (vitamin B(6)), higher levels of choline, and low levels of symmetric dimethylarginine. These data did not show meaningful differences between cases and controls for any other analytes