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Maternal LINE-1 methylation and congenital heart defects in Down syndrome

Background: Down syndrome (DS) is one of the most common chromosomal abnormalities associated with congenital heart defects (CHD) ; cardiac defects are present in approximately 40%-60% of cases. The aim of this study was to determine the association between maternal global DNA methylation and occurrence of CHD in DS. The impact of MTHFR C677T polymorphism and dietary intake of folate on global DNA methylation was analyzed. Patients and methods: The study included 94 mothers of children with DS of maternal origin. Among those mothers, 49% (46/94) have children with DS and CHD (DS-CHD+) and 51% (48/94) of them have children with DS without CHD (DS-CHD- ). Global DNA methylation was analysed in peripheral blood lymphocytes by quantification of LINE-1 methylation using MethyLight method. Genotyping of MTHFR C677T polymorphism was performed by PCR-RFLP. Results: There was no significant difference in values of global DNA methylation between mothers of children with DS-CHD+ and mothers of children with DS-CHD- (P=0.951). Combination of MTHFR C677T genotype/diet significantly influenced global DNA methylation (R2=4.5%, P=0.046). The lowest values of global DNA methylation were determined in mothers with CT+TT genotype and low folate diet. The contribution of these factors was even higher among mothers of children with DS-CHD+ (R2=9.9%, P=0.026), particularly among those who had children with DS and septal heart defect (R2=15.4%, P=0.018). Conclusion: Although, global DNA methylation was not significantly associated with development of CHD in DS, its influence cannot be completely excluded, since the significant impact of MTHFR genotype and diet on global DNA methylation in mothers of DS-CHD+ was determined. Further analyses on larger sample are needed to provide an answer to this question.

LINE-1 methylation; Down syndrome; congenital heart defects

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