Association between maternal single nucleotide polymorphisms in genes regulating glucose metabolism and risk for neural tube defects in offspring

Fu, Yunting; Wang, Linlin; Yi, Dengxia; Jin, Lei; Liu, Jufen; Zhang, Yali; Ren, Aiguo

doi:10.1002/bdra.23332

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…NTDs are recognized to have a complex etiology, mainly involving both genetic and environmental factors. Several observations supported the opinion that genetic factors mainly involve the planar cell polarity (PCP) signaling pathway [13, 14], folate metabolism pathway [15], and glycometabolism pathway [16]. Nuritional factors is the most common environmental factor influencing susceptibility to disease.…”

Section: Discussionmentioning

confidence: 99%

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway

et al. 2019

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BackgroundNeural tube defects (NTDs) are birth defects of the brain, spine, or spinal cord invoked by the insufficient intake of folic acid in the early stages of pregnancy and have a complex etiology involving both genetic and environmental factors. So the study aimed to explore the association between alterations in maternal one-carbon metabolism and NTDs in the offspring.MethodsWe conducted a case-control study to get a deeper insight into this association, as well as into the role of genetic polymorphisms. Plasma concentrations of folate, homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and genotypes and alleles distributions of 52 SNPs in 8 genes were compared for 61 women with NTDs-affected offspring and 61 women with healthy ones.ResultsThere were significant differences between groups with regard to plasma folate, SAM, SAH and SAM/SAH levels. Logistic regression results revealed a significant association between maternal plasma folate level and risk of NTDs in the offspring. For MTHFD1 rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227–5.529; OR = 1.847, 95%CI: 1.047–3.259). For MTHFR rs1801133 polymorphism, mothers having TT and CT genotypes were more likely to affect NTDs in the offspring (OR = 4.105, 95%CI: 1.271–13.258; OR = 3.333, 95%CI: 1.068–10.400). Moreover, mothers carrying T allele had a higher risk of NTDs in the offspring (OR = 1.798, 95%CI: 1.070–3.021). For MTRR rs1801394 polymorphism, the frequency of G allele was significantly higher in cases than in controls (OR = 1.763, 95%CI: 1.023–3.036). Mothers with NTDs-affected children had higher AG genotype in RFC1 rs1051226 polymorphism than controls, manifesting an increased risk for NTDs (OR = 3.923, 95%CI: 1.361–11.308).ConclusionFolic acid deficiency, MTHFD1 rs2236225, MTHFR rs1801133, MTRR rs1801349 and RFC1 rs1051226 polymorphisms may be maternal risk factors of NTDs.

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Section: Discussionmentioning

confidence: 99%

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway

et al. 2019

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“…It was shown that maternal mutations of relevant genes involved in folate metabolism are associated with an increased risk for neural tube or congenital heart defects [170][171][172]. Similar findings were demonstrated for maternal polymorphisms involved in glucose metabolism [173]. Such drastic teratogenic consequences highlight the possible impact maternal genetic deficiencies can have, regardless of any transmission to the offspring.…”

Section: Interaction Of Parental Genes Parental Environment and Fetamentioning

confidence: 68%

Developmental Origins of Disease - Crisis Precipitates Change

Reichetzeder

Putra

et al. 2016

Cell Physiol Biochem

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The concept of developmental origins of diseases has gained a huge interest in recent years and is a constantly emerging scientific field. First observations hereof originated from epidemiological studies, linking impaired birth outcomes to adult chronic, noncommunicable disease. By now there is a considerable amount of both epidemiological and experimental evidence highlighting the impact of early life events on later life disease susceptibility. Albeit far from being completely understood, more recent studies managed to elucidate underlying mechanisms, with epigenetics having become almost synonymous with developmental programming. The aim of this review was to give a comprehensive overview of various aspects and mechanisms of developmental origins of diseases. Starting from initial research foci mainly centered on a nutritionally impaired intrauterine environment, more recent findings such as postnatal nutrition, preterm birth, paternal programming and putative interventional approaches are summarized. The review outlines general underlying mechanisms and particularly discusses mechanistic explanations for sexual dimorphism in developmental programming. Furthermore, novel hypotheses are presented emphasizing a non-mendelian impact of parental genes on the offspring's phenotype.

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“…A few studies have supported the opinion that genetic factors mainly involve the planar cell polarity signaling pathway,[ 32 33 ] folate metabolism pathway,[ 34 ] and carbohydrate metabolism pathway. [ 35 ] However, the exact mechanism is yet not understood clearly.…”

Section: Discussionmentioning

confidence: 99%

MTHFR C677T and MTR A2756G gene polymorphism in neural tube defect patients and its association with red blood cell folate level in Eastern Indian Population

Thakur

Kumar

Singh

et al. 2022

J Indian Assoc Pediatr Surg

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Introduction: Single-nucleotide polymorphism (SNP) is a single-nucleotide change in a deoxyribose nucleic acid (DNA) sequence that occurs in >1% of population. Methylene tetra hydro folate reductase (MTHFR) C677T (rs1801133) and methionine synthase enzyme (MTR) A2756G (rs1805087) are two such SNPs occurring in coding sequence of the respective genes, which are frequently seen with neural tube defects (NTDs). MTHFR and MTR genes are involved in folate metabolism. The folate level in the course of pregnancy is treated as vital in the etiopathogenesis of NTDs. This study aims to explore the association of SNPs of both genes and red blood cell (RBC) folate levels in the predisposition to NTDs. Aims and Objective: The purpose of this investigation was to determine the relationship of NTDs with polymorphisms in MTHFR and MTR genotype and to estimate and compare the RBC folate levels in NTD patients and controls. Materials and Methods: A total of 397 individuals were enrolled (163 patients and 234 controls) for this observational study. Genotyping to find out MTHFR C677T and MTR A2756G was performed by polymerase chain reaction–restriction fragment length polymorphism technique from DNA extracted from the subject's blood. RBC folate level was estimated by chemiluminescence immunoassay method with the same blood sample. Results: The total RBC folate levels were significantly less among cases compared to controls ( P = 0.020). A significant difference for RBC folate was observed between case and control groups of various genotypes of MTHFR C677T, except heterozygote CT ( P = 0.459). Among MTR A2756G, genotypes with only homozygous AA have significant difference ( P = 0.003) for RBC folate levels. Among different types of NTDs, there were no significant differences for RBC folate levels. Among MTHFR C677T, T allele possessed 1.9 times risk compared to C allele for the occurrence of NTDs. In MTR A2756G polymorphism, the odds of developing NTDs were 1.6 times in heterozygous AG compared to homozygous AA. Similarly, the risk for NTDs was three times higher in subjects with both heterozygous AG and CT genotypes compared to wild-type homozygous AA and CC genotypes. Conclusion: The total RBC folate levels were significantly less among cases compared to controls, and the genotypes had no such effect in decrease in RBC folate levels. The presence of mutant allele in homozygous or heterozygous condition for both SNPs had increased risk associated with NTDs.

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Association between maternal single nucleotide polymorphisms in genes regulating glucose metabolism and risk for neural tube defects in offspring

Abstract: The AA genotype in maternal GCKR rs780094 is associated with an increased risk for NTDs and spina bifida in the Chinese population.

Cited by 8 publications

References 43 publications

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway

Association of neural tube defects with maternal alterations and genetic polymorphisms in one-carbon metabolic pathway

Developmental Origins of Disease - Crisis Precipitates Change

MTHFR C677T and MTR A2756G gene polymorphism in neural tube defect patients and its association with red blood cell folate level in Eastern Indian Population

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