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

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.

Association of maternal folic acid supplementation and offspring MTRR gene polymorphism with congenital heart disease: a hospital-based case-control study in Han population

“…The inconsistent results may be explained by racial differences, differences in study design, and the presence of bias. In addition, several studies con rmed that MTRR gene polymorphisms were also associated with a variety of cancers [33][34][35], reproductive disorders[36] and cleft lip and palate [37]. However, most of the previous studies only focused on two loci (i.e., rs1801394 and rs1532268).…”

Association between MTHFR C677T polymorphism and the susceptibility to nonsyndromic cleft lip with or without cleft palate in Chinese Han population: a case-control study and meta-analysis

“…However, publications regarding the association between MTHFR and NSCL/P were inconsistent. Some studies (Li et al, 2020;Luo et al, 2012;Pan et al, 2015;Pan et al, 2012;Rai 2018;Shu et al, 2019;Zhao et al, 2014) reported that MTHFR C677T polymorphism was signi cantly associated with NSCL/P risk in Asian, Caucasian and Mixed populations, whereas Lmani et al (Imani et al, 2020) found that there was no signi cant association based on the ethnicity or the source of cases. And according to Amooee's research (Amooee et al, 2019), the result of strati ed analysis by country of origin revealed a signi cant association in Brazilian, Turkish and Indian populations, but not in US-American and Chinese.…”

ENAM gene polymorphisms associated with dental anomalies in individuals with cleft lip and palate

“…Many genes play a role in craniofacial development and polymorphism may be associated with cleft lip and palate (CLP) 1 . The lack of more detailed definition in phenotype partially explains difficulty in genetic studies on CLP 2 .…”