{"title":"Methylenetetrahydrofolate Reductase Dimer Configuration as a Risk Factor for Maternal Meiosis I-Derived Trisomy 21.","authors":"Jadranka Vraneković, Ivana Babić Božović, Iva Bilić Čače, Bojana Brajenović Milić","doi":"10.1159/000515121","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":13226,"journal":{"name":"Human Heredity","volume":null,"pages":null},"PeriodicalIF":1.1000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000515121","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Heredity","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1159/000515121","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/3/30 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.
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.
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