Maternal and infant gene–folate interactions and the risk of neural tube defects

Abstract

Neural tube defects (NTDs) are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. The authors evaluated maternal or offspring folate-related gene variants and interactions between the gene variants and maternal intake of folates on the risk of NTDs in their offspring. A case-control study was conducted on mothers and/or their fetuses and infants who were born in California from 1999–2003 with an NTD (cases n = 222, including 24 mother-infant pairs) or without a major malformation (controls n = 454, including 186 mother-infant pairs). Maternal intake of folates was assessed by food frequency questionnaire and genotyping was performed on samples from mothers and infants. For mothers in the lowest folate-intake group, risk of NTDs in offspring was significantly decreased for maternal MTHFR SNPs rs1476413, rs1801131 and rs1801133 (odds ratio (OR) = 0.55, 80% confidence interval (CI): 0.20, 1.48; OR = 0.58, 80% CI: 0.24, 1.43; OR = 0.69, 80% CI: 0.41, 1.17, respectively), and TYMS SNPs rs502396 and rs699517 (OR= 0.91, 80% CI: 0.53, 1.56; OR = 0.70, 80% CI: 0.38, 1.29). A gene-only effect was observed for maternal SHMT1 SNP rs669340 (OR = 0.69, 95% CI: 0.49, 0.96). When there was low maternal folate intake, risk of NTDs was significantly increased for infant MTHFD1 SNPs rs2236224, rs2236225 and rs11627387 (OR = 1.58, 80% CI: 0.99, 2.51; OR = 1.53, 80% CI: 0.95, 2.47; OR = 4.25, 80% CI: 2.33, 7.75, respectively) and SHMT1 SNP rs12939757 (OR = 2.01, 80% CI: 1.20, 3.37), but decreased for TYMS SNP rs2847153 (OR = 0.73, 80% CI: 0.37, 1.45). Although power to detect interaction effects was low for this birth defects association study, the gene-folate interactions observed in this study represent preliminary findings that will be useful for informing future studies on the complex etiology of NTDs.

Effect of genetic polymorphisms involved in folate metabolism on the concentration of serum folate and plasma total homocysteine (p-tHcy) in healthy subjects after short-term folic acid supplementation: a randomized, double blind, crossover study

“…Maternal folate deficiency and genetic polymorphisms in folate metabolism have also been linked to neural tube defects (NTDs) in new born babies (Etheredge et al 2012). An attempt to reduce the prevalence of NTDs in the USA, the fortification of wheat flour with folic acid was started in 1998 (US FDA 1996).…”

Myelomeningocele as newborn complication of lupus patient. A singular case.

“…When there are difficulties in its physiological mechanisms may appear neural tube closure defects, with appearance of spina bifida and presence of MMC [15,16]. In the case reported, high levels of glycemia are described during gestation, being evaluated by a specialist who, at the time, considered it appropriate to make only dietary recommendations.…”

“…Both drugs have been approved for the treatment of SLE during pregnancy and have been classified as safe despite there being always a minimal risk of malformations. In the case of azathioprine a possible explanation could be given by the competition with the enzyme xanthine oxidase which would hamper the processes of degradation and assimilation of uric acid, folic acid and B-complex vitamins [14][15][16].…”

“…The administration of vitamin supplements rich in folic acid and B-complex vitamins, especially B12, is one of the measures that have been taken to reduce the appearance of malformations such as MMC [10,15,16]. Countries with higher rates of development The United States of America, Ireland, the United Kingdom, China, Hungary, Chile and Mexico, have managed to reduce the incidence of MMC based on the administration of these supplements during pregnancy, and even nowadays its administration is suggested for a Less than 6 months before conception of pregnancy.…”

“…Countries with higher rates of development The United States of America, Ireland, the United Kingdom, China, Hungary, Chile and Mexico, have managed to reduce the incidence of MMC based on the administration of these supplements during pregnancy, and even nowadays its administration is suggested for a Less than 6 months before conception of pregnancy. The administration of multivitamin supplements is more relevant in patients with NCDs who wish to have a healthy pregnancy [15,16].…”