神经管缺陷相关妊娠中母体选择的叶酸代谢相关基因的多态性

Polymorphisms in Maternal Selected Folate Metabolism-Related Genes in Neural Tube Defect-Affected Pregnancy.

作者信息

Dewelle Winner K, Melka Daniel S, Aklilu Abenezer T, Gebremariam Mahlet Y, Alemayehu Markos A, Alemayehu Dawit H, Woldemichael Tamrayehu S, Gebre Solomon G

机构信息

Department of Biochemistry, School of Medicine, College of Health Sciences, Addis Ababa University, Ethiopia, East Africa.

Biochemistry Division of Basic Sciences, University of Global Health Equity, Kigali, Rwanda, East Africa.

出版信息

Adv Biomed Res. 2023 Jun 30;12:160. doi: 10.4103/abr.abr_103_22. eCollection 2023.

DOI:10.4103/abr.abr_103_22

PMID:37564453

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10410419/

Abstract

BACKGROUND

Neural tube defects (NTDs) are abnormalities of the brain and spinal cord, which occur as a result of failure in neural tube closure during embryogenesis. Causes of NTDs are complex and multiple, with hereditary, lifestyle, and environmental factors appearing to play a role. In spite of their impact on public health, the role genetics play on NTDs in Ethiopia is lacking. In this study, the role of polymorphisms in MTHFR 677C > T (rs1801133), MTHFR 1298A > C (rs1801131), MTRR 66A > G (rs1801394), RFC1 80A > G (rs1051266), and TCN2 776C > G (rs1801198) on the risk of having NTD-affected pregnancy was investigated.

MATERIALS AND METHODS

One hundred women with NTD-affected pregnancy and 100 women with normal pregnancy were included in the study. DNA was extracted from saliva and genotyping for five polymorphisms in four genes was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The departure of the genotype's distribution from Hardy-Weinberg equilibrium (HWE) was evaluated using the x goodness-of-fit test. Frequencies of genotypes and alleles in case and control mothers were determined and differences between relative frequencies were evaluated by the x or the Fisher's exact test.

RESULTS

The statistically significant difference was absent in the genotype and allele frequencies for all the analyzed polymorphisms between cases and controls ( > 0.05).

CONCLUSION

MTHFR 677C > T, MTHFR 1298A > C, MTRR 66A > G, RFC1 80A > G, and TCN2 776C > G polymorphisms lack association with the risk of having a pregnancy affected by NTD. The role of other genes or environmental factors in NTD etiology needs to be investigated.

摘要

背景

神经管缺陷（NTDs）是大脑和脊髓的异常情况，其发生是由于胚胎发育过程中神经管闭合失败所致。NTDs的病因复杂多样，遗传、生活方式和环境因素似乎都发挥着作用。尽管NTDs对公众健康有影响，但在埃塞俄比亚，遗传学在NTDs中所起的作用尚不清楚。在本研究中，调查了亚甲基四氢叶酸还原酶（MTHFR）677C>T（rs1801133）、MTHFR 1298A>C（rs1801131）、甲硫氨酸合成酶还原酶（MTRR）66A>G（rs1801394）、还原型叶酸载体1（RFC1）80A>G（rs1051266）和钴胺素转运蛋白2（TCN2）776C>G（rs1801198）基因多态性对NTDs妊娠风险的影响。

材料与方法

本研究纳入了100例患有NTDs妊娠的女性和100例正常妊娠的女性。从唾液中提取DNA，并通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析四个基因中五个多态性的基因分型。使用χ²拟合优度检验评估基因型分布与哈迪-温伯格平衡（HWE）的偏离情况。确定病例组和对照组母亲的基因型和等位基因频率，并通过χ²检验或费舍尔精确检验评估相对频率之间的差异。