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Global DNA methylation and trisomy 21

This study aimed to determine the association between global DNA methylation and nondisjunction of chromosome 21 during oogenesis. The impact of endogenous and exogenous factors on global DNA methylation was analyzed, including MTHFR C677T polymorphism, gender, age, body mass index, intake of folate through diet, periconceptional folic acid supplementation, smoking, alcohol drinking and medication use. Methods: The study included 94 mothers of children with Down syndrome (DS) of maternal origin and with defined meiotic stage of chromosome nondisjunction and 100 mothers of healthy children with no personal or family history. Global DNA methylation was analyzed in peripheral blood lymphocytes by quantification of LINE-1 methylation using MethyLight method. Genotyping of MTHFR C677T polymorphism was performed by PCR-RFLP. Results: Global DNA methylation in mothers of children with DS was significantly lower than in control mothers (P=0.000), but no significant differences were found regarding the meiotic stage of nondisjunction of chromosome 21. Combination of MTHFR C677T genotype/diet significantly influenced global DNA methylation (R2=4.5%, P=0.046)wherein the lowest values were determined in mothers with CT+TT genotype and low folate diet. Conclusion: Our findings revealed global DNA hypomethylation in mothers of children with DS, suggesting that this is a possible risk factor for nondisjunction of chromosomes 21 during oogenesis.

DNA methylation; global; Nondisjunction; genetic; Down syndrome; MTHFR

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