Metabolic effects of C677T and A1298C mutations at the MTHFR gene in Brazilian children with neural tube defects

2002 ◽  
Vol 318 (1-2) ◽  
pp. 139-143 ◽  
Author(s):  
Andrea L.A Cunha ◽  
Mario H Hirata ◽  
Chong A Kim ◽  
Elvira M Guerra-Shinohara ◽  
Kymio Nonoyama ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Mthfr Gene ◽  
Metabolic Effects ◽  
Brazilian Children

scholarly journals Loci C677T and A1298C of the methylenetetrahydrofolate reductase gene and the risk of neural tube defects in the Kyrgyz population

2019 ◽  
pp. 3-8
Author(s):  
Н.М. Алдашева ◽  
Э.М. Мамбетсадыкова ◽  
Э.Т. Талайбекова ◽  
С.Дж. Боконбаева ◽  
Х.М. Сушанло ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Methylenetetrahydrofolate Reductase ◽  
Strong Association ◽  
Mthfr Gene ◽  
Control Group ◽  
Increased Risk ◽  
Pcr Rflp ◽  
1298C Allele ◽  
Kyrgyz Population

Цель. Изучить ассоциацию полиморфных локусов С677Т и А1298С гена MTHFR с развитием дефектов нервной трубки (ДНТ) у детей киргизской национальности. Методы. В исследование включены 76 детей и их матери. В основную группу вошли 30 детей с пороками невральной трубки, чаще всего в виде изолированной спиномозговой грыжи или в сочетании с другими врожденными пороками развития, а также их матери. 46 детей без ДНТ и их матери составили контрольную группу. Идентификация генотипов полиморфных локусов С677Т и А1298С гена MTHFR проводилась методом анализа полиморфизма длин рестрикционных фрагментов (ПДРФ). Результаты. При анализе распределения генотипов и аллелей полиморфизма А1298С гена MTHFR выявлено, что среди детей с ДНТ статистически значимо чаще встречались гетерозиготный генотип А1298С (χ²=9,67; р=0,0079) и аллель 1298С (χ²=4,17; р=0,04). При наличии генотипа А1298С риск развития ДНТ повышается в 4,71 раза (OR=4,71; p=0,0079), а при наличии аллеля 1298С - в 2,2 раза (OR=2,20; p=0,04). Полиморфный локус С677Т гена MTHFR самостоятельно не был ассоциирован с ДНТ, однако гетерозиготность по двум полиморфным аллелям ассоциирована с ДНТ (χ²=5,60; p=0,018) и существенно повышает относительный риск развития ДНТ (OR=9,75; p=0,018). Заключение. У детей киргизской национальности полиморфный локус А1298С гена MTHFR ассоциирован с развитием дефекта нервной трубки. Комбинированная гетерозиготность (С677Т/А1298С) по обоим полиморфизмам является дополнительным отягощающим фактором. Aim. The aim of the study was to investigated whether polymorphisms С677Т and А1298С of the MTHFR gene are associated with neural tube defects (NTDs) in the Kyrgyz population. Methods. The study included 76 children and their mothers. The study group included 30 children and their mothers, where the child had a neural tube defect, most commonly in the form of an isolated spina bifida or in combination with congenital anomalies. Control group - 46 children without congenital malformations. С677Т and А1298С polymorphisms analysis in the MTHFR gene were performed by PCR-RFLP method. Results. The frequency of the heterozygous A1298C genotype (χ²=9,67; p=0,0079) and 1298C allele (χ²=4,10; p=0,041) of the MTHFR gene was higher in cases than in controls. Child with heterozygous A1298C genotype had a 4,71- fold (OR=4,71; p=0,0079) higher risk of NTDs when compared with those who had the AA genotype. Child carriers of the 1298C allele had a 2,2-fold higher risk of NTDs (OR=2,20; p=0,041). С677Т/А1298С genotypes are more frequent among cases than controls (χ²=5,00; p=0,025). We showed that the combinations of С677Т/А1298С is strong association with NTDs (χ²=5,60; p=0,018). Subjects carriers of the combinations of С677Т/А1298С genotypes had a significant 9,7-fold higher risk of NTDs (OR=9,75; p=0,018). Conclusion. There is significant association between С677Т and А1298С polymorphism in MTHFR gene and neural tube defects in the Kyrgyz population. An increased risk of neural tube defects associated with heterozygous A1298C genotype, 1298C allele and combinations of С677Т/А1298С in MTHFR gene.

Folate, Homocysteine and Neural Tube Defects: An Overview

2001 ◽  
Vol 226 (4) ◽  
pp. 243-270 ◽  
Author(s):  
Nathalie M.J. Van Der Put ◽  
Henny W.M. Van Straaten ◽  
Frans J.M. Trijbels ◽  
Henk J. Blom
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Genetic Risk ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Folate Intake ◽  
Elevated Blood ◽  
Moderate Risk ◽  
Mthfr Polymorphisms ◽  
Increased Risk

Folate administration substantially reduces the risk on neural tube defects (NTD). The interest for studying a disturbed homocysteine (Hcy) metabolism in relation to NTD was raised by the observation of elevated blood Hcy levels in mothers of a NTD child. This observation resulted in the examination of enzymes involved in the folate-dependent Hcy metabolism. Thus far, this has led to the identification of the first and likely a second genetic risk factor for NTD. The C677T and A1298C mutations in the methylenetetrahydrofolate reductase (MTHFR) gene are associated with an increased risk of NTD and cause elevated Hcy concentrations. These levels can be normalized by additional folate intake. Thus, a dysfunctional MTHFR partly explains the observed elevated Hcy levels in women with NTD pregnancies and also, in part, the protective effect of folate on NTD. Although the MTHFR polymorphisms are only moderate risk factors, population-wide they may account for an important part of the observed NTD prevalence.

Frequency of the thermolabile variant C677T in the MTHFR gene and lack of association with neural tube defects in the State of Yucatan, Mexico

2002 ◽  
Vol 62 (5) ◽  
pp. 394-398 ◽  
Author(s):  
L González-Herrera ◽  
G García-Escalante ◽  
I Castillo-Zapata ◽  
J Canto-Herrera ◽  
J Ceballos-Quintal ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Mthfr Gene ◽  
The State

Variants in MTHFR gene and neural tube defects susceptibility in China

2015 ◽  
Vol 30 (4) ◽  
pp. 1017-1026 ◽  
Author(s):  
Yongxin Wang ◽  
Yuan Liu ◽  
Wenyu Ji ◽  
Hu Qin ◽  
Hao Wu ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Mthfr Gene

scholarly journals Gene Expression Profile Associated With Neural Tube Defects Among Infants Attending Muhimbili National Hospital And Muhimbili Orthopaedic Institute In Tanzania

2020 ◽  
Author(s):  
Mariam Sadallah ◽  
Evelyne Neema Assenga ◽  
Charles Pallangyo ◽  
Karim Manji
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Statistical Tests ◽  
Mthfr Gene ◽  
Muhimbili National Hospital ◽  
National Hospital ◽  
Low Expression

Abstract Background Neural tube defects (NTDs) are severe congenital anomalies of the central nervous system. The specific cause is not known, though several factors including gene variants involving the folate metabolism have been implicated in the etiology. This study aimed at identifying the gene expression profile of selected genes known to be associated with NTDs among infants attending Muhimbili National Hospital (MNH) and Muhimbili Orthopaedic Institute (MOI).Methodology We conducted a matched case control study involving infants who were attending MNH and MOI during 6 months of the study period. Each case was matched with two controls by gestational age, sex and birth weight. Whole blood samples were collected from all study participants for genetic analysis. Total RNA was isolated using Qiagen RNA blood mini kit, and reversed transcribed into complementary DNA (cDNA) using Super Script II Reverse Transcriptase cDNA Synthesis kit. Real-time polymerase chain reaction was performed on extracted cDNA by a Light Thermal Cycler 480 machine using specific primers for studied genes to determine their expression levels.Results were analysed by GraphPad Prism 5Software, using Student t-test, and Bonferroni post hoc statistical tests. A p value of < 0.05 was considered to be statistically significant. Results The study recruited 50 cases and 100 controls. Among eight studied genes, we found significantly low expression of Methylenetetrahydrofolate reductase [MTHFR] gene among cases than controls (p=0.006). Expression of others genes were having variations and expressed at very low levels in both cases and controls.Conclusion A low expression level of MTHFR gene was a significant risk factor for the occurrence of NTDs amongst infants attending MNH and MOI.Recommendation: We recommend gene expression analysis to be done on mothers of infants with NTDs to identify those at risk; and further mutational analysis to be done to enhance genetic counseling and therefore to prevent recurrence of NTDs.

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