Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Nonsyndromic Cleft Lip and/or Palate

Waltrick-Zambuzzi, Márcia; Tannure, Patrícia Nivoloni; Vieira, Thays Cristine dos Santos; Antunes, Leonardo Santos; Romano, Fábio Lourenço; Zambuzzi, Willian Fernando; Granjeiro, José Mauro; Küchler, Érika Calvano

doi:10.1590/0103-6440201300394

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…In the second phase, the full‐text review was then conducted on the 71 first‐phase selected citations, which lead to the exclusion of 22 studies. In the end of the two phases, 49 studies fulfilled the inclusion criteria (Antunes et al, ; Araújo et al, ; Araujo et al, ; Bagordakis et al, ; Bezerra et al, ; Brandalize et al, ; Brito, Bassi, & Masotti, ; Brito et al, ; Bufalino et al, ; Cardoso et al, ; Choi et al, ; da Silva, Ribeiro, Cooper, Marazita, & Moretti‐Ferreira, ; de Aguiar et al, ; de Aquino et al, a,b; de Souza et al, ; do Rego Borges et al, ; Ehlers Bertoja, Sampaio Alho, De França, Menegotto, & Miriam Robinson, ; Falagan‐Lotsch et al, ; Filézio et al, ; Fontoura, Silva, Granjeiro, & Letra, ; Gaspar et al, ; Jehee et al, ; Küchler et al, ; Letra, Menezes, Granjeiro, & Vieira, ; Letra, Silva, & Menezes, ; Letra et al, a,b; Machado et al, a,b, ; Menezes, Letra, Ruff, Granjeiro, & Vieira, ; Menezes et al, ; Messetti et al, ; Paranaíba et al, ; Passos‐Bueno et al, ; Sabóia et al, ; Souza, Kowalski, Collares, & Félix, ; Souza, Kowalski, Vanz, Giugliani, & Félix, ; Waltrick‐Zambuzzi et al, ; Zucchero et al, ), but only 11 articles were used in the meta‐analysis (Antunes et al, ; Araújo et al, ; Bagordakis et al, ; Brito et al, ; de Aguiar et al, ; do Rego Borges et al, ; Fontoura et al, ; Gaspar et al, ; Paranaíba et al, ;).…”

Section: Resultsmentioning

confidence: 99%

Potential genetic markers for nonsyndromic oral clefts in the Brazilian population: A systematic review and meta‐analysis

Machado

Toledo

Martelli‐Júnior

et al. 2018

Birth Defects Research

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A large number of genetic markers distributed in several genes/loci was associated with NOC in the Brazilian population, but in general the original studies included limited number of samples and unsatisfactory protocols. The classical risk markers located in IRF6 and 8q24 showed promising results as well as rs1801133 in MTHFR and rs17563 in BMP4, and they should be validated in larger and multicenter studies taking in consideration the variations in the miscegenation of Brazilian population.

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Section: Resultsmentioning

confidence: 99%

Potential genetic markers for nonsyndromic oral clefts in the Brazilian population: A systematic review and meta‐analysis

Machado

Toledo

Martelli‐Júnior

et al. 2018

Birth Defects Research

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“…The significance of genetic locus in folate pathway and folate metabolism involved in disease pathogenesis is not clear [2,3]. Recently, many efforts have been made to find the genetic variants in folate pathway genes such as MTHFR (methylenetetrahydrofolate reductase), MTRR (Methionine synthase reductase), TCN2 (transcobalamin 2), and BHMT (betaine-homocysteine methyltransferase) and their susceptibility to cleft lip [4][5][6][7][8][9][10]. MTHFR plays an important role in primary circulation of folate and catalyzing the reaction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate.…”

Section: Introductionmentioning

confidence: 99%

“…The four genetic missense variations 677C>T in MTHFR (rs1801133), 66A>G in MTRR (rs1801394), 776C>G in TCN2 (rs1801198), and 716 G>A in BHMT (rs3733890) have influence on protein function (Table 1), and have been reported to be associated with cleft lip. However, there are different conclusions regarding the influence of these SNPs in different populations [4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

SNPs in folate pathway are associated with the risk of nonsyndromic cleft lip with or without cleft palate, a meta-analysis

Jia

et al. 2020

Bioscience Reports

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Background: Prenatal intake of folic acid is important for prevention of NSCL/P (nonsyndromic cleft lip with or without cleft palate). Associated genes in folate pathway are major enzymes of folic acid metabolism that is crucial for preventing birth defects. The present meta-analysis aims to investigate the association between four SNPs in folate pathway genes and the risk of NSCL/P. Methods: Comprehensive bioinformatics analysis was used to predict the functional pathogenicity of genetic variation. The PubMed, Embase database and Google Scholar were searched by two researchers. Stata 11.0 software was used to analyze the results. Subgroup analysis was carried out to assess the influence of genetic background. Sensitivity analysis, regression analysis and publication analysis were also conducted to enhance the strength of our results. Results: It is estimated that the probability of two missense mutation rs1801133 in MTHFR and rs1801394 in MTRR are more likely to be damaging by bioinformatics analysis. A significant association between rs1801133 and risk of NSCL/P in two genetic models: TT genotype vs CC genotype (OR = 1.333 95%CI = 1.062–1.674, P = 0.013), and recessive model (OR = 1.325 95%CI = 1.075–1.634, P = 0.008). A significant protective association between rs1801394 GG genotype and NSCL/P in Asian (GG vs AA, OR = 0.520 95%CI = 0.321–0.841, P = 0.008) was observed. Meta-regression, sensitivity analysis, and publication bias analysis confirmed that the results of the present study were statistically significant. Conclusions: The present study identified that rs1801133 in MTHFR is associated with the risk of NSCL/P, and rs1801394 GG genotype in MTRR play a protective role in Asian. Further, larger studies should be performed to confirm these findings.

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“…Recently, many efforts have been made to find the genetic polymorphisms in folate pathway genes such as MTHFR, MTRR, TCN2, and BHMT and their susceptibility to cleft lip [4][5][6][7][8][9][10]. [12].…”

Section: Introductionmentioning

confidence: 99%

“…The four genetic missense variations C677T in MTHFR (rs1801133), A66G in MTRR (rs1801394), C776G in TCN2 (rs1801198), and G716A in BHMT (rs3733890) have influence on protein function (Table 1), and have been reported to be associated with cleft lip. However, there are different conclusions regarding the influence of these SNPs in different populations [4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Two SNPs rs1801133 and rs1801394 in folate pathway are associated with the risk of nonsyndromic cleft lip with or without cleft palate

Li¹,

Xu²,

Jia³

et al. 2019

Preprint

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Background Prenatal intake of folic acid is important for prevention of nonsyndromic cleft lip with or without cleft palate (NSCL/P). Associated genes in folate pathway are major enzymes of folic acid metabolism that is crucial for preventing birth defects. The present study aims to investigate the association between four single nucleotide polymorphisms (SNPs) in folate pathway genes and the risk of NSCL/P. Methods Comprehensive bioinformatics analysis was used to predict the functional pathogenicity of genetic variation. The PubMed, Embase database and Google Scholar were intensively searched by two researchers to ascertain all relevant studies. Stata 11.0 software was used to analyze the results. Subgroup analysis was carried out to assess the influence of genetic background. Sensitivity analysis, regression analysis and publication analysis were also conducted to enhance the strength of our results. Results It is estimated that the probability of two missense mutation rs1801133 in MTHFR and rs1801394 in MTRR are more likely to be damaging by bioinformatics analysis. A total of 34 publications were included in the present study analysis. Our results showed a significant association between rs1801133 and risk of NSCL/P in two genetic models: TT allele vs CC allele (OR=1.333 95%CI=1.062-1.674, P =0.013), and recessive model (OR=1.325 95%CI=1.075-1.634, P =0.008). A significant association between rs1801394 and the risk of NSCL/P in Asian (GG allele vs AA allele, OR=0.520 95%CI=0.321-0.841, P =0.008) was also observed. Meta-regression, sensitivity analysis, and publication bias analysis confirmed that the results of the present study were statistically significant. Conclusions The present study highlights two SNPs rs1801133 in MTHFR and rs1801394 in MTRR, associated with the increasing risk of NSCL/P. Further, larger studies should be performed to confirm these findings.

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Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Nonsyndromic Cleft Lip and/or Palate

Cited by 8 publications

References 25 publications

Potential genetic markers for nonsyndromic oral clefts in the Brazilian population: A systematic review and meta‐analysis

Potential genetic markers for nonsyndromic oral clefts in the Brazilian population: A systematic review and meta‐analysis

SNPs in folate pathway are associated with the risk of nonsyndromic cleft lip with or without cleft palate, a meta-analysis

Two SNPs rs1801133 and rs1801394 in folate pathway are associated with the risk of nonsyndromic cleft lip with or without cleft palate

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