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.

A case-control study investigating the effect of MTHFR C677T variant on performance of elite athletes

2020 ◽  
Vol 20 ◽  
Author(s):  
Ayse Feyda Nursal ◽  
Serbulent Yigit ◽  
Husniye Rustemoglu ◽  
Abdullah Cenikli
Keyword(s):  
Athletic Performance ◽  
Methylenetetrahydrofolate Reductase ◽  
Elite Athletes ◽  
Mthfr C677t ◽  
Mthfr Gene ◽  
Control Group ◽  
Genotype Distribution ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Strength Of Association

Objective: Increased level of plasma homocysteine (Hcy) is a potential risk factor for several multi-system diseases. The Methylenetetrahydrofolate reductase (MTHFR) gene C677T variant has been established as an important genetic determinant of hyperhomocysteinemia. There are conflicting reports about the effects of physical activity on plasma Hcy. Therefore, the main aim of this study was to investigate whether the MTHFR C677T variant affects the elite athletic performance. Methods: This study was carried out on 214 individuals (114 elite athletes and 100 sedentary controls). Genotyping was performed using PCR- RFLP method. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results: There was a significant difference between the athletes and the control group in genotype distribution and allele frequency of the MTHFR C677T variant. MTHFR C677T CC genotype and C allele were more prevalent in elite athletes than those in the sedentary controls (p =0.007, OR: 2.16, 95%:1.26-3.70; p=0.009, OR: 1.84, 95%:1.18-2.89, respectively). The control group had a higher MTHFR C677T CT genotype than the athletes had (p=0.019, OR: 0.51, 95%:0.30-0.88). There was no deviation from HWE for the MTHFR C677T variant in the groups. Conclusion: Our findings support that there is an association between the MTHFR C677T C allele and athletic performance among the elite Turkish athletes.

Risk Factors of Neural Tube Defects in a Sample of Iranian Population From Southern Iran: A Hospital-based Investigation

2020 ◽  
Vol 5 (3 And 4) ◽  
pp. 117-124
Author(s):  
Mohammad Sadegh Masoudi ◽  
◽  
Negin Hadi ◽  
Fariborz Ghaffarpasand ◽  
Mohammadreza Askarpour ◽  
...  
Keyword(s):  
Risk Factors ◽  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Clinical Findings ◽  
Iranian Population ◽  
Control Group ◽  
Geographical Variations ◽  
Increased Risk ◽  
Baseline Characteristics

Background and Aim: The risk factors of the Neural Tube Defects (NTD) have been previously described but there are ethnic and geographical variations. Data from the Iranian population is still scarce. The objective of the current study was to investigate the NTDs risk factors in a large sample of Iranian patients admitted to a single center.  Methods and Materials/Patients: This case-control study was performed within five years from 2012 to 2017 in Namazi Hospital of Shiraz, a tertiary referral center for neonatal anomalies in the south of Iran. One hundred newborns with NTDs were included in the study as the case group and 200 healthy newborns as the control group. We recorded the baseline characteristics including the maternal variables (age, weight, height, previous pregnancy and gravidity, gestational age), newborn information (birth weight, clinical diagnosis, clinical findings in the examination, and clinical findings in radiologic test) and medical history of the perinatal period. Results: The baseline characteristics of the mothers were matched in both groups. NTDs were associated with lower folic acid intake during pregnancy (66% vs. 78%; P=0.030; OR 95% CI=1.82) and before pregnancy (P=0.002; OR95% CI=2.36). The prevalence of NTD was significantly higher in patients who lived in hot climates (P=0.001). Conclusion: Taking adequate folic acid supplements before and during pregnancy can reduce the risk of NTDs in the Iranian population. Hot climate zones were associated with an increased risk of NTDs in Iran.

Impact of 5,10-methylenetetrahydrofolate reductase gene polymorphism on neural tube defects

2010 ◽  
Vol 6 (4) ◽  
pp. 364-367 ◽  
Author(s):  
Poomagame Narasimhamurthy Harisha ◽  
B. Indira Devi ◽  
Rita Christopher ◽  
Tumkur Puttasiddhappa Kruthika-Vinod
Keyword(s):  
Risk Factor ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Methylenetetrahydrofolate Reductase ◽  
Test Group ◽  
Control Group ◽  
South Indian Population ◽  
Chi Square ◽  
South Indian ◽  
Significant Difference

Object Neural tube defects (NTDs) are among the most common congenital malformations worldwide. Their etiology and exact mechanisms of development are incompletely understood. Many enzymes involved in folate metabolism and the genes encoding these enzymes have been studied as candidates in their etiology. A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene—a C→T transition at nucleotide 677—is one among them. The mutation results in substitution of alanine by valine at a functionally important site in the enzyme. It has been shown to be a risk factor for development of NTDs in certain populations. The present study was conducted to evaluate the role of MTHFR 677 C→T mutation as a risk factor for NTD in the South Indian population and to determine the relative importance of the genotypes in the affected child and its mother. Methods Blood samples were collected from the test and the control groups. The test group consisted of children with NTDs and their mothers, while the control group consisted of apparently healthy controls. MTHFR C677T polymorphism in the 3 groups was determined by polymerase chain reaction and restriction fragment length polymorphism studies. Comparison of polymorphism in the 3 groups was using the chi-square test. Results There was a significant difference in the prevalence of MTHFR 677 C→T mutation among the 3 groups (p = 0.002). The risk conferred by the TT genotype in the child was statistically significant (OR 12.625, 95% CI 1.430–111.465). In the mothers, however, although there was an increased prevalence of the mutation compared with the control individuals, the difference was not statistically significant (p = 0.152). Conclusions The MTHFR 677TT genotype is considered to be a definite risk factor for development of NTDs. It is the TT genotype status of the developing embryo, rather than the TT genotype status of its mother, that is the critical genetic determinant of MTHFR-related NTD risk.

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