| Abstrakt: |
Objective: The objective was to investigate the association between maternal methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, crucial for DNA methylation, and risk of offspring aneuploidy. Methods: MTHFR gene polymorphisms 677C>T and 1298A>C were determined by polymerase chain reaction based method, in 163 women with offspring aneuploidy and 155 women with healthy children. Five genetic models were used to assess risk, according to the type of aneuploidy and the age of women at conception. Results: MTHFR 677TT genotype and T allele were significantly more prevalent among women with offspring aneuploidy, with an increased risk of aneuploidy demonstrated under a recessive (OR 3.499), homozygote (OR 3.456) and allele contrast model (OR 1.574). The more prominent association was found with sex chromosome aneuploidies and trisomy 13/18, and also in women ≤35 years at conception. No association was observed between 1298A>C polymorphism and risk of offspring aneuploidy, although synergistic effect of two polymorphisms increase the risk of aneuploidy, primarily amplifying the 677T allele effects (p < 0.001). Conclusion: Maternal MTHFR 677C>T gene polymorphism, alone or in combination with another 1298A>C polymorphism, appears to be a substantial risk factor for offspring aneuploidy in Montenegro population, especially for sex chromosome aneuploidies and trisomy 13/18, and among younger women. Key points: What's already known about this topic? Polymorphisms in folate pathway genes, especially the MTHFR 677C>T, with consequent DNA hypometilation, have been identified as possible risk factors for trisomy 21 in certain populations.Large geographical variations with conflicting results are shown. What does this study add? This is the first clinical and genetic study on Montenegrin population and one of several in Mediterranean region, providing evidence of maternal MTHFR 677C>T gene polymorphism as a substantial risk factor for offspring aneuploidy, not only 21 trisomy but also trisomy 13/18 and sex chromosome aneuploidies. [ABSTRACT FROM AUTHOR] |
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