MTHFR C677T、MTHFR A1298C 和 MTRR A66G 多态性与突尼斯父母神经管缺陷的关联。

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

机构信息

Faculté des Sciences de Bizerte, Université de Carthage, Bizerte, Tunisia,

UR 06/ SP14 Troubles du développement embryo-fœtal et placentaire, Service d'embryo-fœtopathologie, Centre de Maternité et de Néonatologie La Rabta et de la Faculté de Médecine de Tunis, Université El Manar II, Tunis, Tunisia,

出版信息

Pathobiology. 2019;86(4):190-200. doi: 10.1159/000499498. Epub 2019 Jun 25.

DOI:10.1159/000499498

PMID:31238314

Abstract

OBJECTIVE

This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population.

METHODS

Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software.

RESULTS

MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53-10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05).

CONCLUSION

Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

摘要

目的

本研究旨在探讨 5,10-亚甲基四氢叶酸还原酶（MTHFR C677T 和 A1298C）和蛋氨酸合成酶还原酶（MTRR A66G）基因多态性与突尼斯人群神经管缺陷（NTD）的关系。

方法

采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，用限制性内切酶进行基因分型。根据 SPSS 软件的关联分析，比较 NTD 胎儿母亲和父亲与匹配对照的等位基因和基因型频率。

结果

MTHFR（C677T、A1298C）和 MTRR A66G 多态性被发现是母亲组 NTD 胎儿的保护因素。此外，三个野生型等位基因 C677/A1298/A66 的组合使 NTD 的发病率增加了四倍（p=0.004，OR=3.96，95%CI：1.53-10.23）。在父亲组中，MTHFR C677T 是 NTD 的危险因素。然而，MTHFR A1298C、MTRR A66G 与这种异常的发生之间没有关联。对 MTHFR C677T 和 MTRR A66G 多态性的分析表明，病例母亲的隐性和显性基因型之间的维生素 B12 水平有显著差异（p<0.05）。