engleski

Polymorphisms in folate pathway genes as risk factors for congenital heart defects in Down syndrome

Background: Congenital heart defects (CHD) are one of the most common abnormalities occurring in 40% -60% of Down Syndrome (DS) cases. Most commonly, these are septal defects, including atrial septal defect, ventricular septal defect and complete atrioventricular canal. Studies have shown that phenotypic variability in a individuals with DS may contribute to various genetic factors. The polymorphisms of genes involved in folate metabolism are the most significant candidate genes for CHD. However, the correlations between genes and CHD were inconsistent in various reports. Aim: The study aimed to determine the spectrum of CHD among DS and to evaluate the effects of polymorphisms of 5-methyltetrahydrofolate homocysteine methyltransferase reductase (rs1801394) and 5, 10-methylenetetrahydrofolate reductase (rs1801133 and rs1801131) genes on CHD in DS. Subjects and method: A total of 155 individuals with DS have been enrolled in this study. Genotyping of polymorphisms was performed by PCR-RFLP. Statistical significance was considered at P<0.05. Results: CHDs was present in 50% of participants and higher frequencies of CHDs was observed among females than males (54% vs. 46%, P=0.077). Atrial septal defect was most common presents in females as well in males (32% vs. 22%). No significant differences in distribution and frequencies of investigated polymorphisms were observed according to the presence of CHD (P  0, 05). Conclusions: The occurrence of CHD, particularly in female gender of DS individuals is similar as documented in literatures. The disruption of the folate pathway do not contributes to the incidence of CHD among individuals with DS in our study.

congenital heart defects, Down syndrome, folate genes

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