MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies

Yu, Di; Zhuang, Zhulun; Wen, Zhongyuan; Zang, Xiaodong; Mo, Xuming

doi:10.1186/s13052-017-0425-1

Cited by 14 publications

(12 citation statements)

References 31 publications

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“…The latter is involved in the transformation of HCY to methionine, releasing tetrahydrofolate, which is decreasing the level of plasma HCY [10]. Therefore, the correlation between polymorphism of MTHFR gene and CHDs has become research focuses [11][12][13]. However, there is a great controversy reports about the relationship between the maternal MTHFR rsl801133 and rsl801131 polymorphism and their offspring CHDs [12,[14][15][16].…”

Section: Discussionmentioning

confidence: 99%

“…However, there is a great controversy reports about the relationship between the maternal MTHFR rsl801133 and rsl801131 polymorphism and their offspring CHDs [12,[14][15][16]. Some of them considered that rs1801133 and rs1801131 were related with the risk of CHDs [12,13]. But some studies suggested that there is no association between the parents' polymorphism of MTHFR rs1801133 and children' CHDs [14].…”

Section: Discussionmentioning

confidence: 99%

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Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

et al. 2020

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The aim of this study is to evaluate the relationship between maternal single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) gene with plasma homocysteine (HCY) level and offspring congenital heart diseases (CHDs). 338 mothers with offspring CHDs as case group and 306 mothers of normal children as control group were recruited. Their pregnant histories were interviewed by questionnaire and the MTHFR rsl801133 and rsl801131 were genotyped. The case–control analysis was used to find out the relationship between maternal SNPs of MTHFR gene and offspring CHDs. And the plasma HCY concentration of the mothers of CHDs children was detected. This case–case study was intended to find out the relevance between maternal HCY level and SNPs of MTHFR gene. There were significant differences in the gender of children, occupation of mothers, family history with CHDs, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHDs group and control group (P < 0.05). MTHFR rs1801133 was significantly associated with their offspring CHDs in mothers. The polymorphism of maternal MTHFR rs1801133 increased plasma HCY level, especially the homozygous mutation. Besides the environmental factors, our results suggested that the maternal MTHFR rs1801133 polymorphism might be a risk factor of their offspring CHDs, which may be due to the hyperhomocysteinemia by abnormal metabolism of HCY.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

et al. 2020

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“…Previous studies mainly focused on the genetic polymorphisms of MTHFR gene at rs1801133 and rs1801131. It has confirmed that genetic variants of these two SNPs were significantly associated with lower activity of MTHFR, which can further reduce the concentration of folate in plasma while increase the level of homocysteine [ 21 , 27 – 29 ]. There were some studies showing genetic variant of rs1801133 in mothers was a risk factor for fetal CHD in the Chinese Han population [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Sun

Wang

Huang

et al. 2021

BMC Cardiovasc Disord

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Background Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. Methods A case–control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. Results Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95–19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77–9.71]). And six haplotypes of G–C (involving rs4846048 and rs2274976), A–C (involving rs1801133 and rs4846052), G–T (involving rs1801133 and rs4846052), G–T–G (involving rs2066470, rs3737964 and rs535107), A–C–G (involving rs2066470, rs3737964 and rs535107) and G–C–G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene–gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. Conclusions Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

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“…They found a significant association between the MTHFR C677T polymorphism and CHD risk in the maternal analysis (OR: 1.52, 95% CI: 1.09–2.11, p = 0.01) [ 25 ]. In another study by Yu et al, 16 eligible studies concerning MTHFR A1298C polymorphism and CHD, involving 2207 cases and 2364 controls, were included in the meta-analysis; the results suggested that the CC genotype of MTHFR A1298C is a risk factor for CHDs [ 26 ]. As well as these previous studies, our results demonstrated that the MTHFR C677T and MTHFR A1298C polymorphisms are also strongly related to the risks of CTDs and of certain types of CTD, including TOF, DORV, PTA, and IAA.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population

et al. 2018

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BackgroundConotruncal heart defects (CTDs) are a subgroup of congenital heart defects that are considered to be the most common type of birth defect worldwide. Genetic disturbances in folate metabolism may increase the risk of CTDs.MethodsWe evaluated five single-nucleotide polymorphisms (SNPs) in genes related to folic acid metabolism: methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), solute carrier family 19, member 1 (SLC19A1 G80A), methionine synthase (MTR A2576G), and methionine synthase reductase (MTRR A66G), as risk factors for CTDs including various types of malformation, in a total of 193 mothers with CTD-affected offspring and 234 healthy controls in a Chinese population.ResultsLogistic regression analyses revealed that subjects carrying the TT genotype of MTHFR C677T, the C allele of MTHFR A1298C, and the AA genotype of SLC19A1 G80A had significant 2.47-fold (TT vs. CC, OR [95% CI] = 2.47 [1.42–4.32], p = 0.009), 2.05–2.20-fold (AC vs. AA, 2.05 [1.28–3.21], p = 0.0023; CC vs AA, 2.20 [1.38–3.58], p = 0.0011), and 1.68-fold (AA vs. GG, 1.68 [1.02–2.70], p = 0.0371) increased risk of CTDs, respectively. Subjects carrying both variant genotypes of MTHFR A1298C and SLC19A1 G80A had a higher (3.23 [1.71–6.02], p = 0.0002) increased risk for CTDs. Moreover, the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms were found to be significantly associated with the risk of certain subtypes of CTD.ConclusionsOur data suggest that maternal folate-related SNPs might be associated with the risk of CTDs in offspring.

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MTHFR A1298C polymorphisms reduce the risk of congenital heart defects: a meta-analysis from 16 case-control studies

Cited by 14 publications

References 31 publications

Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

Study on Maternal SNPs of MTHFR Gene and HCY Level Related to Congenital Heart Diseases

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring

Genetic variation in folate metabolism is associated with the risk of conotruncal heart defects in a Chinese population

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