Jadranka Vraneković1, Ivana Babić Božović2, Iva Bilić Čače3, Bojana Brajenović Milić1. 1. Department of Biology and Medical Genetics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia. 2. Clinical Institute of Genomic Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia. 3. Department of Pediatrics, Clinical Hospital Center Rijeka, University of Rijeka, Rijeka, Croatia.
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.
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.
Authors: Carla Talita Azevedo Ginani; Jefferson Romáryo Duarte da Luz; Saulo Victor E Silva; Fabio Coppedè; Maria das Graças Almeida Journal: Medicine (Baltimore) Date: 2022-01-21 Impact factor: 1.889