04 September 2015 : Clinical Research
Polymorphisms in MTHFD1 Gene and Susceptibility to Neural Tube Defects: A Case-Control Study in a Chinese Han Population with Relatively Low Folate Levels
Jian WuAE, Yihua BaoBF, Xiaolin LuCD, Lihua WuBF, Ting ZhangG, Jin GuoA, Jian YangAFDOI: 10.12659/MSM.895155
Med Sci Monit 2015; 21:2630-2637
Abstract
BACKGROUND: The polymorphism of methylenetetrahydrofolate dehydrogenase (MTHFD1) has been reported as a risk factor for neural tube defects (NTDs). In the present study, we aimed to investigate whether the single-nucleotide polymorphisms (SNPs) of MTHFD1 gene are associated with NTDs in a Chinese population and to determine their mechanism of action.
MATERIAL AND METHODS: MTHFD1 gene was scanned in a total of 270 NTDs cases and 192 healthy controls by using next-generation sequencing (NGS) method. After quality control procedures, 208 selected SNP sites in MTHFD1 gene were enrolled for follow-up statistical association analyses. Functional analyses were also performed for significant SNPs through bioinformatics analysis. Folic acid levels of brain tissue in available NTDs cases and healthy controls (113 and 123, respectively) were measured. Statistical and bioinformatics analyses were performed to investigate the relationship between SNPs in MTHFD1 and susceptibility to NTDs.
RESULTS: Statistical analysis showed that 2 independent SNPs, rs1956545 and rs56811449, confer the risk of NTDs (P value=0.0195, OR (odds ratio)=1.41, 95% CI (confidence interval)=1.06–1.88; P value=0.0107, OR=0.56, 95% CI=0.36–0.87). The haplotype GGGG, which consists of 4 SNPs (rs2236225, rs2236224, rs1256146, and rs6573559), is also associated with risk of NTDs (P value=0.0438, OR=0.7180, 95% CI=0.5214–0.9888). The risk allele C of rs1956545 is also associated with decreased folic acid levels in the brain (P value=0.0222, standard beta=–0.2238, 95% CI=–0.4128 – –0.0349) according to analysis in the subset of NTDs cases and healthy controls. Bioinformatics analysis indicates that rs1956545 and rs56811449 are within ENCODE regulatory regions, the open chromatin regions of blastula Trophoblast cell line, and histone-marked region of brain astrocyte cell line.
CONCLUSIONS: The polymorphism of SNP loci rs1956545 and rs56811449 as well as a haplotype in MTHFD1 gene could serve as an indicator for the occurrence of NTDs in Chinese population and some specific genotypes of the loci may have lower risk of developing NTDs.
Keywords: Brain - metabolism, Alleles, Case-Control Studies, Computational Biology - methods, Fetus - pathology, Folic Acid - chemistry, Genetic Predisposition to Disease, Haplotypes, High-Throughput Nucleotide Sequencing, Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics, Neural Tube Defects - genetics, Odds Ratio, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Quality Control, Risk Factors, Stillbirth
Editorial
01 February 2025 : Editorial
Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-SmokersDOI: 10.12659/MSM.948255
Med Sci Monit 2025; 31:e948255
In Press
Clinical Research
Predicting Cerebral Small Vessel Disease Burden Based on Thromboelastography in Patients with Acute Ischemi...Med Sci Monit In Press; DOI: 10.12659/MSM.946303
Clinical Research
Long-Term Outcomes of Implanon in Managing Adenomyosis: A 3-Year Prospective StudyMed Sci Monit In Press; DOI: 10.12659/MSM.945972
Laboratory Research
Linear Dimensional Accuracy in Maxillomandibular Records: A Comparative Study of Scannable and Transparent ...Med Sci Monit In Press; DOI: 10.12659/MSM.947265
Clinical Research
Efficacy of King's Combined Uterine Suture in Managing Placenta Accreta: A Retrospective AnalysisMed Sci Monit In Press; DOI: 10.12659/MSM.945826
Most Viewed Current Articles
17 Jan 2024 : Review article 6,969,932
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research 701,896
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Mar 2024 : Editorial 25,741
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...DOI :10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
28 Jan 2024 : Review article 20,253
A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and FutureDOI :10.12659/MSM.943912
Med Sci Monit 2024; 30:e943912