Association of reduced folate carrier gene polymorphism and maternal folic acid use with neural tube defects.
ABSTRACT This study was designed to investigate whether the risk for neural tube defects (NTDs) was associated with reduced folate carrier gene (RFC1 A80G) polymorphism and/or with the interaction between the RFC1 gene and maternal periconceptional use of folic acid. One hundred four nuclear families with NTDs and 100 non-malformed control families were sampled to investigate the potential interaction between maternal or the offspring's RFC1 (A80G) genotypes and the maternal periconceptional use of folic acid through a population-based case-control study. RFC1 (A80G) genotypes were detected using PCR-restricted fragment length polymorphism (PCR-RFLP). Mother who had the GG genotype and did not take folic acid had an elevated risk for NTDs (OR = 5.43, 95% CI = 1.68-18.28) as compared to the mother who had AA or GA genotype and took maternal periconceptional folic acid. The interactive coefficient was 1.12 between maternal GG genotype and the periconceptional folic acid non-use. The risk for having an infant with NTDs was 8.80 (95% CI = 2.83-28.69) for offspring with the GG genotype, as compared to the offspring with AA or GA genotype among the mothers who did not take folic acid supplements. The interactive coefficient was 1.45 for offspring with the GG genotype and without maternal periconceptional supplementation of folic acid. Our findings suggest that there is a potential gene-environment interaction on the risk of NTDs between maternal or offspring RFC1 GG genotype and maternal periconceptional intake of folic acid. The RFC1 is likely to be an important candidate gene in folate transportation and RFC1 GG genotype (A80G) may be associated with an increased risk for NTDs in this Chinese population.
Article: Genetic studies of myelomeningocele.[Show abstract] [Hide abstract]
ABSTRACT: Myelomeningocele is one of the major congenital malformations involving the central nervous system. It is caused by a disruption of the neural tube closure, which is completed at 3-4 weeks of gestation. Multidisciplinary approach is necessary to treat and support this malformation which is a huge burden to the patient, family, and the society. This is a characteristic anomaly that it is known that taking folic acid during the periconceptional period, it is possible to reduce the risk of having a neural tube defect (NTD). Although folate fortification had dramatically reduced the incidence, it was not possible to diminish the risk. To date, many studies have been conducted focusing on candidate genes related to folate and glucose metabolism. We will describe a brief review of genetic etiology of candidate genes of metabolic pathways of folate and glucose, animal models of NTDs, and finally recent studies of microRNA.Child s Nervous System 09/2013; 29(9):1417-25. · 1.24 Impact Factor
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ABSTRACT: PURPOSE: To explore the relationship between genetic polymorphisms in reduced folate carrier 1 (RFC-1), cystathionine b-synthase (CBS), two key genes in folate metabolism, and the risk of Down syndrome in China. METHODS: Genomic DNA was isolated from the peripheral lymphocytes of 104 mothers born children with Down syndrome and 184 age-matched control mothers. Polymerase chain reaction and restriction-fragment length polymorphism were used to examine the polymorphisms of RFC-1 A80G, CBS T833C and the relationship between these genotypes and the risk of Down syndrome was analyzed. RESULTS: We found that there were significant differences between RFC-1 G80G, CBS C833C polymorphisms among mothers of children with Down syndrome than among control mothers, with odds ratio of 1.51 (95 % CI 1.05-2.18), 1.53 (95 % CI 1.07-2.18) respectively. The combined presence of RFC1 mutant alleles and the CBS homozygous mutant allele (15/104) was associated with a 4.81-fold increased risk of having a child with Down syndrome (95 % CI 1.82-12.68, P = 0.0007). CONCLUSIONS: We concluded that RFC-1 and CBS gene mutation alleles are related to Down syndrome, and women with mutation RFC-1 G80G, CBS C833C OR combined with RFC-1 A80G and CBS 833TT genotype increase the risk of Down syndrome in China.Archives of Gynecology 02/2013; · 1.28 Impact Factor
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ABSTRACT: Abstract Objective To investigate the association of 12 single nucleotide polymorphisms (SNPs) in folate metabolic genes with congenital heart disease (CHD). Methods 160 children with CHD and 188 control children were enrolled. 12 SNPs related to folate metabolism, including CBS-C699T, DHFR-c594+59del19, FOLH1-T1561C, CBS-C699T, DHFR-c594+59del19, GSTO1-C428T, MTHFD-G878A and -G1958A, MTHFR-C677T and -A1298C、MTR-A2756G, MTRR-A66G, NFE2L2-ins1+C11108T, RFC1-G80A, TCN2-C776T and TYMS-1494del6, were genotyped by SNaPShot genotyping technology and confirmed by Sanger sequencing. Results There were two SNPs including NFE2L2-ins1+C11108T and GST01-C428T and two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD- G1958A, RFC1-G80A and MTR-A2756G), which might increase the risk of CHD, and DHFR-c594+59del19 might decrease the risk of CHD. The CT genotype of NFE2L2-ins1+C11108T, OR=2.15(95%CI= [1.07, 4.32], P<0.05). The CT + TT genotype of NFE2L2-ins1+C11108T, OR=1.98 (95%CI= [1.00, 3.93], P<0.05). The TT genotype of GST01-C428T, OR=3.49，(95CI%= [1.06,11.5], P<0.05). The GG genotype of DHFR-c594+59del19, OR=0.46(CI%= [0.24, 0.87], P<0.05). The AG + GG genotype of DHFR-c594+59del19, OR=0.53(CI%= [0.29, 0.96], P<0.05). The ratios of the two compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD- G1958A, RFC1-G80A and MTR-A2756G) in CHD are higher than that in control, P<0.05 (OR=2.968, 95%CI= [1.022, 8.613]). Conclusions The CT genotype of NFE2L2-ins1+C11108T and the TT genotype of GST01-C428T are susceptible factors for CHD. The AG, GG and (AG+GG) genotypes of DHFR-c594+59del19 are protective genotypes for CHD. Compound mutants for (MTHFD-G1958A, MTHFR-C677T and MTR-A2756G) and (MTHFD-G1958A, RFC1-G80A and MTR-A2756G) may increase the risk of CHD.The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 05/2013; · 1.36 Impact Factor