Methylenetetrahydrofolate Reductase Dimer Configuration as a Risk Factor for Maternal Meiosis I-Derived Trisomy 21.

IF 1.1 4区生物学 Q4 GENETICS & HEREDITY

Human Heredity Pub Date : 2020-01-01 Epub Date: 2021-03-30 DOI:10.1159/000515121

Jadranka Vraneković, Ivana Babić Božović, Iva Bilić Čače, Bojana Brajenović Milić

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引用次数: 4

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

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亚甲基四氢叶酸还原酶二聚体配置是母体减数分裂衍生的21三体的危险因素。

背景:有证据表明，甲基四氢叶酸还原酶(MTHFR)酶的二聚体构型可能会因C677T和A1298C位点单体的多态性而不稳定。这些多态性可能导致稳定的(CCAA, CCAC, CCCC)和不稳定的(CTAA, CTAC, TTAA)酶二聚体构型。目的:本研究的目的是评估母源性21三体儿童母亲的MTHFR酶二聚体结构和叶酸饮食摄入量与减数分裂不分离阶段的关系。方法:本研究共纳入119例母源性游离21三体患儿的母亲。21三体患儿出生时母亲的平均年龄为32.3±6.4岁(范围16-43岁)。所有的母亲都是白种人。利用21q染色体着丝粒到端粒的短串联重复标记确定了21三体亲本起源和非分离减数分裂阶段。采用PCR-RFLP分析MTHFR C677T和A1298C多态性。结果:MTHFR基因型组合CTAA、CTAC和TTAA在减数分裂I (MI)不分离的母亲组中出现频率增加(p = 0.007)。研究参与者之间在饮食和生活习惯方面没有发现差异。结论:在孕前未服用叶酸补充剂的CTAA、CTAC和TTAA MTHFR基因型组合患者发生21号染色体不分离性心肌梗死的风险高4.6倍。

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来源期刊

Human Heredity 生物-遗传学

CiteScore

2.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gathering original research reports and short communications from all over the world, ''Human Heredity'' is devoted to methodological and applied research on the genetics of human populations, association and linkage analysis, genetic mechanisms of disease, and new methods for statistical genetics, for example, analysis of rare variants and results from next generation sequencing. The value of this information to many branches of medicine is shown by the number of citations the journal receives in fields ranging from immunology and hematology to epidemiology and public health planning, and the fact that at least 50% of all ''Human Heredity'' papers are still cited more than 8 years after publication (according to ISI Journal Citation Reports). Special issues on methodological topics (such as ‘Consanguinity and Genomics’ in 2014; ‘Analyzing Rare Variants in Complex Diseases’ in 2012) or reviews of advances in particular fields (‘Genetic Diversity in European Populations: Evolutionary Evidence and Medical Implications’ in 2014; ‘Genes and the Environment in Obesity’ in 2013) are published every year. Renowned experts in the field are invited to contribute to these special issues.