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

2019 ◽  
Author(s):  
Qiuyan Li ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
Tahir Zaib ◽  
Wenjing Sun ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Nucleotide Polymorphisms ◽  
Bias Analysis ◽  
Single Nucleotide ◽  
Folate Pathway ◽  
Embase Database

Abstract Background Prenatal intake of folic acid is important for prevention of nonsyndromic cleft lip with or without cleft palate (NSCL/P), genes participant in folate pathway are crucial for preventing birth defects. The present study aims to investigate the associations between four single nucleotide polymorphisms (SNPs) in folate pathway genes and the risk of NSCL/P. Methods Prediction by bioinformatics was conducted to assess the function of genetic variation. The PubMed, Embase database and Google Scholar were searched by two researchers to identify all relevant studies. Stata 11.0 software was used to calculate the results. Subgroup analysis was conducted to assess the influence of the genetic background. Sensitivity analysis, regression analysis and publication analysis were conducted to improve the strength of the results. Results Two genetic variations rs1801394 in MTRR gene and rs1801133 in MTHFR were predicted damaging. A total of 34 publications were included in the present analysis. The results showed that there were a significant association between rs1801133 and NSCL/P risk 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) and there were a significant association between rs1801394 and NSCL/P risk in Asian (GG allele vs AA allele, OR=0.520 95%CI=0.321-0.841, P=0.008). Meta-regression, sensitivity analysis, and publication bias analysis confirmed that the results of the present study were statistically robust. Conclusions This present study suggests that rs1801133 of the MTHFR gene and rs1801394 of the MTRR gene are risk factors for NSCL/P. Additional, larger studies should be performed to confirm these findings.

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

2019 ◽  
Author(s):  
Qiuyan Li(Former Corresponding Author) ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
Komal Saleem ◽  
Tahir Zaib ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Folic Acid ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Bioinformatics Analysis ◽  
Recessive Model ◽  
Nucleotide Polymorphisms ◽  
Bias Analysis ◽  
Single Nucleotide ◽  
Folate Pathway

Abstract 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.

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

2020 ◽  
Vol 40 (3) ◽  
Author(s):  
Qiuyan Li ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
Komal Saleem ◽  
Tahir Zaib ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Folic Acid ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Protective Role ◽  
Recessive Model ◽  
Bias Analysis ◽  
Folate Pathway

Abstract 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.

scholarly journals Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations

2019 ◽  
Vol 33 ◽  
pp. 205873841985857 ◽  
Author(s):  
Francesco Carinci ◽  
Annalisa Palmieri ◽  
Luca Scapoli ◽  
Francesca Cura ◽  
Francesco Borelli ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Folic Acid Supplementation ◽  
Nucleotide Polymorphisms ◽  
Orofacial Clefts ◽  
Single Nucleotide ◽  
Candidate Gene Association ◽  
Folate Pathway ◽  
Family Based ◽  
Gene Association Study

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background.

Association of single nucleotide polymorphisms in WNT genes with the risk of nonsyndromic cleft lip with or without cleft palate

2018 ◽  
Vol 58 (4) ◽  
pp. 130-135 ◽  
Author(s):  
Houshang Rafighdoost ◽  
Mohammad Hashemi ◽  
Hossein Asadi ◽  
Gholamreza Bahari
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals MTHFR and MDR1 Gene Polymorphisms in Yakut Patients with Non-Syndromic Orofacial Clefts

2021 ◽  
Vol 11 (4) ◽  
pp. 576-580
Author(s):  
Aleksandra Diakonova ◽  
Nadezhda Pavlova ◽  
Vladislav Alekseev ◽  
Lyubov Mironova ◽  
Khariton Kurtanov ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Gene Polymorphisms ◽  
Cleft Lip ◽  
Significant Risk ◽  
Rflp Analysis ◽  
Recessive Model ◽  
Mthfr Gene ◽  
Homozygous Genotype ◽  
Increased Risk ◽  
The Republic

The aim of our study was to investigate the relationship between the MDR1 and MTHFR gene polymorphisms and non-syndromic cleft lip with or without cleft palate (NSCL/P) in the Yakut population in the Republic of Sakha (Yakutia). Methods and Results: The sample of examined persons consisted of 60 children with NSCL/P. The NSCL/P group was divided into the CLP (cleft lip with cleft palate) subgroup (n=31), CLO (cleft lip only) subgroup (n=14), and CPO (cleft palate only) subgroup (n=15). The comparison group (control) included 174 healthy volunteers who did not have relatives with OFCs. The study of the MDR1 rs1045642 SNP and the MTHFR rs1801133 SNP was performed by PCR and RFLP analysis. Analysis of the frequency distribution of alleles and genotypes depending on the severity of clefts showed that the carriage of the TT homozygous genotype of the MDR1 rs1045642 SNP was associated with significant risk for the development of NSCL/P (OR=2.52, 95% CI: 1.19-5.32, P=0.02). Analysis of the recessive model (TT vs CC + TC) also found a significant risk of NSCL/P with the TT genotype carriage (OR=2.20, 95% CI: 1.06-4.57, P=0.04). Analysis of the over-dominant model (TC vs TT + CC) showed that the heterozygous TC genotype had a protective effect (OR=0.41; 95% CI: 0.22-0.77, P=0.01) on the development of NSCL/P. Subgroup analysis according to NSCL/P subtypes (CLO, CPO and CLP) showed that the MDR1 rs1045642 SNP was significantly associated with a high risk of CPO in three genetic models: heterozygous [(TT vs TC): OR=5.03; 95% CI: 1.55-16.32; P=0.01], recessive [(TT vs CC + TC): OR=3.96; 95% CI: 1.32-11.95; P=0.02], and over-dominant [(TC vs TT + CC): OR=0.23; 95% CI: 0.08-0.66; P=0.01]. Conclusion: A study of two SNPs in the MDR1and MTHFR genes revealed a statistically significant increased risk for NSCL/P in carriers of the TT genotype of the MDR1 rs1045642 SNP.

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