rs10925260

Abstract Background To investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population. Methods The subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group). Results The levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father’s exposure to organic solvents, folic acid deficiency, and mother’s diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor. Conclusion Folic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.

2022 · Xusen Yang, Guofeng Fan, Zengliang Wang, Shaoshan Li, Hu Qin, Yun Wang, Xiaohu Ma, Wenyu Ji, Yongxin Wang, Xusen Yang, Guofeng Fan, Zengliang Wang, Shaoshan Li, Hu Qin, Yun Wang, Xiaohu Ma, Wenyu Ji, Yongxin Wang

Neural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.

2014 · Faith Pangilinan, Anne M Molloy, James L Mills, James F Troendle, Anne Parle-McDermott, Denise M Kay, Marilyn L Browne, Emily C McGrath, Hatice Ozel Abaan, Marie Sutton, Peadar N Kirke, Michele Caggana, Barry Shane, John M Scott & Lawrence C Brody

The aim of this research was to investigate the role of genetic and nutritional variation within the folate-mediated one-carbon network in relation to cardiovascular disease risk. The enzymes serine hydroxymethyltransferase 1 (gene name SHMT1) and methylenetetrahydrofolate reductase (gene name MTHFR) regulate key reactions in folate-mediated one-carbon metabolism. We investigated the effect of the SHMT1 rs1979277 SNP and the SHMT1 rs1979277 - MTHFR rs1801133 interaction in two epidemiologic cohorts. In the Nurses' Health Study, the MTHFR rs1801133 variant genotypes were associated with an increased CVD risk, and there was an interaction between SHMT1 and MTHFR such that the association of MTHFR rs1801133 CT genotype (vs. CC; the TT genotype could not be evaluated) was stronger in the presence of the SHMT1 rs1979277 TT genotype. In the Health Professionals FollowUp Study, the MTHFR rs1801133 genotype was not associated with CVD risk nor was there an interaction with SHMT1 rs1979277. Next, using data from the Normative Aging Study, 330 SNPs in 52 genes were studied in relation to cardiovascular disease biomarkers. Using a nominal significance threshold of P[LESS-THAN OR EQUAL TO]0.005, 20 SNPs were associated with homocysteine, 8 with Alu methylation, and 1 with LINE-1 methylation. Using a more stringent false discovery rate threshold, SNPs in FTCD, SLC19A1, and SLC19A3 genes were associated with plasma homocysteine, gene x vitamin B-6 interactions were identified for Alu and LINE-1 methylation, and epistatic interactions involving the MTHFR rs1801133 SNP were identified for the plasma homocysteine phenotype. Finally, the SNPs were prospectively evaluated for their association with cardiovascular disease in a U.S. population studied prior to mandatory folate fortification. Using a nominal significance threshold of P[LESS-THAN OR EQUAL TO]0.005, 8 SNPs were associated with CVD risk. Using a more stringent false discovery rate threshold, a polymorphism in the GGH gene was associated with reduced CVD risk. A gene x folate interaction was identified (MAT2B) and two gene x vitamin B-12 interactions were identified (BHMT and SLC25A32). Hypotheses related to SHMT1 were explored and significant gene x gene interactions were identified. Overall, genetic variation in folate-mediated one-carbon metabolism, other than the wellknown effects of the MTHFR 677 C[RIGHTWARDS ARROW]T rs1801133, is predictive of cardiovascular disease risk.

2011 · Susan M. Wernimont