Meta-analysis of the association between methylenetetrahydrofolate reductase A1298C polymorphism and non-syndromic cleft lip and palate based on five genetic models
10.3760/cma.j.cn113903-20230725-00046
- VernacularTitle:基于5种遗传模型评估亚甲基四氢叶酸还原酶A1298C多态性与非综合征性唇腭裂相关性的meta分析
- Author:
Mengyue HUO
1
;
Hua MEI
1
;
Yuheng ZHANG
1
;
Dan SONG
1
;
Chun XIN
1
Author Information
1. 内蒙古医科大学附属医院新生儿科，呼和浩特 010050
- Publication Type:Journal Article
- Keywords:
Cleft lip;
Cleft palate;
Methylenetetrahydrofolate reductase;
Polymorphism;
Meta-analysis
- From:
Chinese Journal of Perinatal Medicine
2024;27(12):1024-1034
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To evaluate the association between methylenetetrahydrofolate reductase ( MTHFR) A1298C polymorphism and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P). Methods:Embase, Web of Science, MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (Central), Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.gov, China Biomedical Literature Database (CBLD), VIP Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Yiigle were searched up to February 28, 2023. The search formula was "nonsyndromic cleft lip and/or cleft palate OR nonsyndromic cleft lip with or without palate OR NSCL/P" AND "5,10-methylenetetrahydrofolate reductase OR methylenetetrahydrofolate reductase OR MTHFR" AND " A1298C OR 1298A>C OR rs1801131 OR polymorphism". Taking NSCL/P patients and control groups as the research objects, we collected and described the research on MTHFR A1298C gene polymorphism and NSCL/P susceptibility under five genetic models (allelic model, homozygous comparison model, heterozygous comparison model, dominant comparison model, and recessive comparison model). Literature screening and quality evaluation were conducted based on inclusion and exclusion criteria, and meta-analysis was performed using Review Manager 5.3 software. Subgroup analysis was carried out according to race, control source, and genotyping method. Results:A total of 24 studies meeting the inclusion criteria were included, involving 8 841 cases, with 3 761 in the NSCL/P group and 5 080 in the control group. In five genetic models, there was no association between MTHFR A1298C polymorphism and the risk of NSCL/P (allele model: OR=1.07, 95% CI: 1.00-1.15, I 2=49%, P=0.06; homozygous comparison model: OR=1.06, 95% CI: 0.90-1.26, I 2=23%, P=0.48; heterozygous comparison model: OR=1.05, 95% CI: 0.95-1.15, I 2=59%, P=0.36; dominant comparison model: OR=1.04, 95% CI: 0.95-1.14, I 2 =58%, P=0.34; recessive comparison model: OR=1.04, 95% CI: 0.89-1.23, I 2=22%, P=0.60). Only in the allele genetic model was there a significant association between MTHFR A1298C polymorphism and the risk of NSCL/P in the Asian population ( OR=1.15, 95% CI: 1.01-1.31, I 2=62%, P=0.04). There was no association between MTHFR A1298C polymorphism and the risk of NSCL/P in other races or any genetic model. In the heterozygous comparison genetic model, when the control group cases were hospital-based, there was an association between MTHFR A1298C polymorphism and the risk of NSCL/P in the population ( OR=1.15, 95% CI: 1.02-1.30, I 2=69%, P=0.03). Regardless of the genotyping method used, there was no association between MTHFR A1298C polymorphism and the risk of NSCL/P. All funnel plots were symmetrical, indicating no significant publication bias in this meta-analysis. Sensitivity analysis showed that no single study would reverse the overall results. Conclusions:MTHFR A1298C polymorphism is not associated with NSCL/P susceptibility in the general population. However, in Asians, MTHFR A1298C polymorphism is significantly associated with an increased risk of NSCL/P.
