Vraneković Jadranka, Babić Božović Ivana, Bilić Čače Iva, Brajenović Milić Bojana
Department of Biology and Medical Genetics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
Clinical Institute of Genomic Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia.
Hum Hered. 2020;85(2):61-65. doi: 10.1159/000515121. Epub 2021 Mar 30.
Evidence suggests that the dimer configuration of methylenetetrahydrofolate reductase (MTHFR) enzyme might be destabilized by polymorphisms in monomers at the positions C677T and A1298C. It has been observed that these polymorphisms may lead to stable (CCAA, CCAC, CCCC) and unstable (CTAA, CTAC, TTAA) enzyme dimer configurations.
The aim of this study was to evaluate the association of the MTHFR enzyme dimer configuration and folate dietary intake with the stage of meiotic nondisjunction in mothers of children with maternally derived trisomy 21.
A total of 119 mothers of children with maternally derived free trisomy 21 were included in the study. The mean maternal age at the time of the birth of the child with trisomy 21 was 32.3 ± 6.4 (range 16-43) years. All mothers were Caucasian. Parental origin of trisomy 21 and meiotic stage of nondisjunction was determined using short tandem repeat markers spanning from the centromere to the telomere of chromosome 21q. The MTHFR C677T and A1298C polymorphism was evaluated by PCR-RFLP.
Increased frequency of the MTHFR genotype combinations CTAA, CTAC, and TTAA was found in the group of mothers with meiosis I (MI) nondisjunction (p = 0.007). No differences were found between study participants regarding dietary and lifestyles habits.
The risk for MI nondisjunction of chromosome 21 was 4.6-fold higher in cases who had CTAA, CTAC, and TTAA MTHFR genotype combinations and who did not used folic acid supplements in the preconception period.
有证据表明，亚甲基四氢叶酸还原酶（MTHFR）的二聚体结构可能会因单体在C677T和A1298C位点的多态性而变得不稳定。据观察，这些多态性可能导致稳定的（CCAA、CCAC、CCCC）和不稳定的（CTAA、CTAC、TTAA）酶二聚体结构。
本研究旨在评估MTHFR酶二聚体结构和叶酸膳食摄入量与母源21三体综合征患儿母亲减数分裂不分离阶段之间的关联。
本研究共纳入119名母源游离21三体综合征患儿的母亲。21三体综合征患儿出生时母亲的平均年龄为32.3±6.4（范围16 - 43）岁。所有母亲均为白种人。使用跨越21号染色体q臂着丝粒到端粒的短串联重复标记来确定21三体综合征的亲本来源和不分离的减数分裂阶段。通过PCR - RFLP评估MTHFR C677T和A1298C多态性。
在减数分裂I（MI）不分离的母亲组中，发现MTHFR基因型组合CTAA、CTAC和TTAA的频率增加（p = 0.007）。研究参与者在饮食和生活习惯方面未发现差异。
具有CTAA、CTAC和TTAA MTHFR基因型组合且在孕前未使用叶酸补充剂的病例中，21号染色体MI不分离的风险高4.6倍。
