engleski

FUNCTIONAL DNMT3B PROMOTER POLYMORPHISM (rs1569686) AND RISK FOR CONGENITAL HEART DEFECTS IN DOWN SYNDROME

The DNMT3B gene codes for DNA methyltransferase 3b (DNMT3b), a protein required for genome-wide de novo methylation during the early stage of embryonic development. Evidence suggested that impaired DNA methylation could be a risk factor for congenital heart defects (CHD). Down syndrome (DS) is one of the most common chromosomal abnormalities associated with congenital heart defects (CHD), with approximately 40 – 60% of cases showing cardiac defects. The most common CHD phenotypes in DS are congenital malformations of cardiac septa, such as atrioventricular septal defects (AVSDs), ventricular septal defects (VSDs), atrial septal defects (ASDs), and tetralogy of Fallot (TOF). The purpose of this study was to analyze the frequency of the phenotype of CHD as well as allele and genotypes association of functional DNMT3B promoter polymorphism −579 G > T (rs1569686) on the development of CHD in DS. The case-control study included 102 CHD+ Down syndrome cases and 88 non- syndromic CHD cases. The median of the ages for CHD+DS cases was 2 years [0 - 27] and for the control group was 7 years [0 - 32]. Demographic data and phenotype of CHD were collected from medical records of participants after parents and guardians gave their written consent. Genomic DNA was isolated from different types of tissue using a commercial kit and quantified by spectrophotometry. Genotype analysis was performed by PCR-RFLP method. Statistically higher frequencies of AVSD and VSD were detected in a group of CHD+DS than controls (P=0.0044 ; P=0.0225). Study results showed a statistically lower frequency of the DNMT3B rs 1569686 TT genotype (OR = 0.40 ; 95% CI: 0.18 – 0.86 ; P=0.020) in CHD+DS cases compared with controls. AVSD and VSD were the most common CHD phenotypes in DS, which were consistent with the literature. Lower frequencies of DNMT3B (rs1569686) TT genotype in- group CHD+DS suggested that those genotype could decreased risk of CHD in DS individuals. Further ongoing studies will better explain those results.

Down syndrome, Dnmt3b, congenital heart defects

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