Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis

Huaxiang Zhao; Jieni Zhang; Mengqi Zhang; Feng Deng; Leilei Zheng; Hui Zheng; Feng Chen; Jiuxiang Lin

doi:10.12688/f1000research.6425.2

Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis

F1000Res. 2015 Jun 4:4:142. doi: 10.12688/f1000research.6425.2. eCollection 2015.

Authors

Huaxiang Zhao¹, Jieni Zhang¹, Mengqi Zhang¹, Feng Deng², Leilei Zheng³, Hui Zheng¹, Feng Chen⁴, Jiuxiang Lin¹

Affiliations

¹ Department of Orthodontics, Peking University School and Hospital of Stomatology, Peking, 100081, China.
² Bybo Dental Group, Beijing, 100062, China.
³ Department of Orthodontics, Affiliated Hospital of Stomatology, Chongqing Medical University, Chongqing, 401147, China.
⁴ Laboratory Center, Peking University School and Hospital of Stomatology, Peking, 100081, China.

Abstract

Aims: To investigate the association between the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism rs 2236225 (c.1958G>A) and susceptibility to non-syndromic cleft of the lip and/or palate (NSCL/P).

Methods: An extensive literature review has been conducted using PubMed, Web of Science, Cochrane Library, Google Scholar, the China National Knowledge Infrastructure (CNKI), and Wanfang Database for eligible researches. The terms for searching were "cleft lip OR cleft palate OR CLP OR CL/P OR oral facial cleft OR OFC" AND "methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 OR methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase OR MTHFD1 OR MTHFD". Two independent researchers screened, evaluated and extracted the data of included studies. The pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated by random effects model under five gene models. Subgroup, sensitivity analysis and publication bias were also assessed.

Results: Ten case-control studies have been included in the systematic review and eight studies have been considered for the meta-analysis. Overall, the MTHFD1 polymorphism rs2236225 and the risk of NSCL/P showed pooled OR (95% CI) of 1.02 (0.86-1.21) under allelic model. A higher degree of heterogeneity was observed in Asian countries (I (2) = 75.6%) compared to non-Asian countries (I (2) = 48.9%). Similar consequence appeared in the subgroup of children (I (2) = 78.6%) compared with that of mothers (I (2) = 0.0%). There was no significant difference in the publication bias by the Begg's funnel plot (P = 0.711) and Egger's regression test (P = 0.746).

Conclusion: Our assessment suggested there was no significant association between the MTHFD1 polymorphism rs 2236225 (c.1958G>A) and the susceptibility to NSCL/P. Further investigations using a large sample size and a more advanced technique should be adopted to reach a more precise conclusion in the future.

Keywords: MTHFD1; Meta-analysis; NSCL/P susceptibility; Polymorphisms.

Grants and funding

This work was supported by grants 81200762 from National Natural Science Foundation of China; Program for the National Clinical Key Subject, Natural Science Foundation of China (81271183, 81470772); the Medical Scientific Research Project of Chongqing (20141013).