The Association Studies Of Four Single Nudeotide Polymorphisms In MECP2 Gene With Pervasive Developmental Disorders And It’s Aberrant Behaviors

Background and objectiveThe MECP2 gene is located in Xq28 of human chromosomes. The gene encodes mythyl-CpG-binding protein 2 (MeCP2) which is a member of methylation CpG binding protein family and plays an important role in the process of DNA methylation regulating gene transcription. In addition, abnormal expression of the gene affects the balance of excitatory synaptic transmission. In the previous studies, the MECP2 gene has been considered as one of susceptility genes for several neuropsychological diseases such as autism, schizophrenia, etc. In the present study, we will explore the relationships between MECP2 gene and PDDs by comparing the differences of MECP2 gene polymorphisms(rs2734647, rs2239464, rs2071569, rs61748381) between PDDs patients and normal controls. Furthermore, we also intend to reveal the genetic mechanism of MECP2 gene on the aberrant behaviors in PDDs patients.Methods80 DSM-IV criteria defined PDDs of Chinese Han and 89 normal controls were enrolled in the study and were extracted venous blood. rs2734647, rs2239464, rs2071569 and rs61748381 of MECP2 gene were genotyped by TaqMan allelic discrimination technology. Using Conners Index of Hyperactivity and Aberrant Behavior Checklist to assess the aberrant behaviors of PDDs patients. Meanwhile, demographic information of patients, such as age, sex, age of onset and the onset of symptoms were also collected.Results1. Statistically significant differences of three kind of genotypes frequencies were found between PDDs and control group in the rs2734647 and rs2071569 polymorphisms of MECP2 gene (all P<0.05). T/T and T/C genotypes frequencies of PDDs group were inferior to the control group, whereas C/C genotype frequency were superior to the controls group in the rs2734647 polymorphism. Similarly, A/A and A/G genotypes frequencies of PDDs group were inferior to the control group, whereas G/G genotype frequency were superior to the controls group in the rs2071569 polymorphism.2. There were strong Linkage Disequilibrium among four polymorphisms of MECP2 gene in PDDs patients, and significant occurrence differences were found through case-control analysis in several haplotypes constructed by 4 genetic loci (all P<0.05).3. MECP2 gene had an influence on aberrant behaviors. Higher T allele frequency of rs2734647 and higher A allele frequency of rs2239464 were found in patients with self-injury behaviour compared to patients without self-injury behaviour. Higher C allele frequency of rs2734647 and higher G allele frequency of rs2239464 were found in patients with stereotyped speech compared to patients without stereotyped speech (all P<0.05). Furthermore, rs2734647 and rs2239464 also had an influence on the severity of aberrant behaviors. Patients possessed of at least one C allele of rs2734647 and patients possessed of at least one A allele of rs2239464 had a higher score in the stereotyped speech subscale(all P<0.05).Conclusions1. MECP2 gene might be a susceptibility gene for PDDs in Chinese Han patients of Yunnan Province.2. There were strong Linkage Disequilibrium among rs2734647、rs2239464、 rs2071569 and rs61748381 in PDDs patients. Several haplotypes constructed by 4 genetic loci were more common in patients with PDDs which further suggested that MECP2 gene might be a susceptibility gene of PDDs.3、The genetic polymorphisms of rs2734647 and rs2239464 in MECP2 gene might influence the occurrence and severity of aberrant behaviors in patients with PDDs.