Author + information
- Recep Eroz1,
- Mesut Okur2,
- Mehmet Selcuk Bektas3,
- Suleyman Gulsen3,
- Anzel Bahadır4,
- Yasin Türker5 and
- Cemalettin Gunes2
Down syndrome (DS) is a genetic disorder that results in extra genetic material from chromosome 21 and seen in patients with congenital heart defects (CHD). Approximately 40%-50% of patients with Down syndrome have a heart defect. CHD affects 6–8 babies in every 1000 live births and connect to fetal loss. It was reported that the frequencies of CHD were ranging from 16-65% in DS.
The gene which encoding the endothelial isoform of nitric oxide synthase (eNOS) is placed in the long arm of chromosome 7 and includes 26 exons spanning 21 kb of genomic DNA. Nitric oxide (NO) is synthesized from L-arginine by eNOS. To the best of our knowledge there is no study to determine the relation between CHD and eNOS polymorphisms in DS cases. So, we aim to investigate the relationship between eNOS polymorphisms (exon 894 G/T, promoter -786T/C and intron G10T) and cardiac lesions to determine whether this polymorphism was associated with CHD in cases with DS.
Material And Methods
50 DS cases (22 girls and 28 boys) were included in the current study. The study was confirmed by local ethics committee. In all participants, transthoracic M-mode, two-dimensional, pulsed-wave, continuous-wave and color Doppler echocardiographic examinations were performed using a General Electric Vingmed Vivid 7 (GE Vingmed Ultrasound AS, Horten, Norway) using 2.5-3.5MHz transducers. Blood samples were collected in tubes containing ethylenediamine tetra-aceticacid (EDTA) and total DNA was isolated via phenol-chloroform extraction methods. The eNOS single nucleotide polymorphisms (SNPs) were detected by PCR-RFLP methods.
The mean age of cases was 27.78 ± 31.02 month old. The cardiac evaluation results of cases were: 11 normal, 5 with total atrioventricular septal defect (AVSD), 9 with atrial septal defect (ASD), 9 with ventricular septal defect (VSD), 9 with patent ductus arteriosus (PDA)+ASD, 2 with PDA + Aortic Regurgitation (AR)+ Mitral Regurgitation (MR), 2 with tetralogy of Fallot (TOF) and 3 with ASD+VSD. According to cardiac lesions, the distributions of eNOS genotypes were given in Table 1. The differences between cases who have not a cardiac lesions (named normal in the text) and cases with ASD, PDA+ASD and PDA+AR+MR were meaningful for eNOS promoter (-786T/C) polymorphism (p<0.05) For eNOS exon (894 G/T) polymorphism, the differences among normal and cases with Total ASVD, ASD, VSD, PDA+ASD, PDA+AR+MR and ASD+VSD were meaningful (p<0.05). Conversely these two polymorphisms, there were not a significant differences between normal and cases with at least one cardiac lesion for Intron G10T polymorphism (p>0.05).
It may be said that there is a relation between CHD and both of eNOS promoter -786T/C and exon 894 G/T polymorphisms in cases with DS. eNOS polymorphisms may be used as a tool to obtain preliminary knowledge about the risk of CHDs during prenatal routine screening in DS cases.