The investigation of MEF2C and CREB1 gene polymorphism relationship in patients with down syndrome

Down syndrome, also termed as trisomy 21, is the most commonly seen cause of mental retardation and is a well-known anomaly related to chromosome 21. Its incidence varies from 1: 600 to 1:1000 live births. Among the genes selected for the study, CERB1 is a transcription factor of 69 kbp belonging to CREB gene that is located on chromosome 2q32.3-q34. MEF2C with band length of 200.723 kbp belongs to MEF2 gene that is located on chromosome 5q14.3. In our study, it was aimed to investigate CREB1 and MEF2C gene polymorphisms; to compare their frequencies with healthy controls and to evaluate possible relationship between alleles found to be significantly related to Down syndrome and cardiac malformations commonly seen in Down syndrome. The study included 100 children with Down syndrome and 100 healthy children. The frequencies of CREB1 and MEF2C gene polymorphism were determined and compared in cases with Down syndrome and control subjects. In addition, casual relationship between gene polymorphisms and anatomic abnormalities related to Down syndrome (congenital heart anomalies) were also studied. Of children with Down syndrome, 58 (58%) were girls whereas 42 (42%) were boys with mean age of 3.19±3.79 months. Mean maternal age was found as 36.86±6.67. It was found that there was VSD in 18%, ASD in 18%, PDA in 11% and AVSD in 7% of the cases. Significant differences were detected between the patient and control groups when frequencies of rs4675690, rs2551640, rs10932201, rs2709376, rs7594560 alleles on CREB1 and rs11951031, rs12521522, rs17421627 on MEF2C genes were compared (p<0.05). When the relationship of allele frequencies of the patient and control groups with cardiac malformations was analyzed for rs467590 gene region belonging to CREB1, it was found that there was significant difference in allele distribution between patients with or without ASD (p<0.05). In conclusion, in the study population including Down syndrome cases from Elazığ region, it was found that ASD and VSD were most commonly encountered anomalies while AVSD had lowest incidence; that there were significant differences in the distribution of 3 distinct alleles in CREB1 rs4675690 gene region between cases with Down syndrome and controls; and that the difference in allele distribution might have a role in Down syndrome cases with ASD.