Drug Dependence Relation Analysis Of Susceptibility Genes And Autism Susceptibility Gene Mutation Screening

As a known transcription repressor, Methyl-CpG binding protein2(MECP2) comprises two functional domains:methyl DNA binding domain and transcription repression domain. MECP2, which acts as a multifunctional nuclear protein in several cellular aspects(such as the chromatin remodelling, regulation of transcription, RNA splicing and so on), may play important roles in the process of neural development. Recent researches show that MECP2gene mutation is implicated in neurodevelopmental disorder, including Rett syndrome, autism and mental retardation. So MECP2gene has become a hotspot in the study of the relationship between the genotype of the susceptible gene and the human neurodevelopmental diseases.Drug addiction has become a prominent social and medical problem at home and abroad. Long-term drug addiction, not only damages the physical and mental health of the patients, but also can infect AIDS and induce crime, is a serious social unstable factor. Drug addiction is a chronic relapsing brain disease which has the main feature of loss of self control and forced repeated use of drug, it is both affected by genetic and environmental factors. Pedigree investigation finds that the genetic rate of drug dependence is as high as54%. People gradually pay more attention to the genetic factors in drug dependence. In recent years, the drug dependence research has made considerable progress, but its mechanism is still not completely clear, although many therapeutic methods have acted a few, the overall effect is poor. Only the biological mechanism is thoroughly elucidated, we can find more effective treatments and prevention methods. Studies have shown that MECP2and BDNF gene are susceptible genes of drug dependence. The existing researches mostly involve in the physiology and morphology of addiction, the association studies between gene polymorphism and drug dependence have not been reported yet.In the present study, we explored the association between methyl-CpG binding protein2(MECP2) gene polymorphisms and heroin addiction, so that we could better understand the genetic mechanisms of heroin addiction. MECP2and BDNF gene were sequenced in32health controls to identify the polymorphisms. SNPs were genotyped in331heroin addicts and325healthy controls using the method of SNaPshot. According to average drug use dosage per day, male heroin addicts were divided into two subgroups. Haploview4.2and SPSS15.0software were used to analyze the association between these polymorphisms and heroin addiction. The results showed that no significant difference in3SNPs allele and genotype frequencies were observed between heroin addicts and controls. The G allele frequency of rs189253298was significantly higher in low dosage group compared with high dosage group(P=0.012). This indicated that the polymorphism rs189253298of MECP2gene was associated with heroin dosage in drug addicts. Individuals with allele G of rs189253298used low amount of heroin every day, so the G allele was a protective factor. A significant difference in rs11030102of BDNF gene allele and genotype frequencies were observed between heroin addicts and controls. The genotype frequencies of rs11030101and rs7124442were significantly different in low dosage group compared with high dosage group(P=0.033, P=0.032). This suggested that there was a relationship between the polymorphism rs11030102of BDNF gene and heroin dependence, also between the polymorphism rs11030101and rs7124442of BDNF and heroin dosage in drug addicts. Individuals with allele T of rs11030101or G of rs7124442used low amount of heroin every day, the G allele and T allele were protective factors.Autism spectrum disorder(ASD), which generally appears in infancy, is a pervasive developmental disorder that has the basic clinical features of language barriers, social obstacles and stereotyped narrow interests, it is often associated with mental retardation, perception, emotional abnormality and so on. It affects seriously the children’s physical and mental development. Now it is believed that ASD is caused by many factors including genetic, neurochemical, viral infection, immune system and other factors. The genetic factor occupies an important position in the pathogenesis of autism. Recent epidemiological studies have found that the numbers of patients with autism are increasing year by year. The male to female ratio of4:1in ASD suggests the involvement of the X chromosome in the etiology of ASD. In addition to autism and Rett syndrome, which both belong to pervasive developmental disorder(PDD), have many similar clinical manifestations. According to these knowledges, it is inferred that autism and RTT may have some common pathogenesis. At present, it is confirmed that MECP2gene is the main pathogenic gene of RTT, so the role of MECP2gene mutation in autism become a hotspot of research. In this study, MECP2gene was sequenced in a cohort of288ASD patients and384controls. We found five missense mutations(T197M, G232A, H371R, E394K, G428S). The functional study found that these mutations didn’t affect the correct localization of MECP2protein in cells. Real-Time PCR test showed that T197M and G232A were serious transcriptional inhibition mutations. The other three mutations were not entirely transcriptional suppressor mutations, they may be related to other functions. In addition, we also detected the copy number variation of MECP2gene in288ASD cases. Two MECP2deletions were identified in two patients with autism. These findings suggest that mutations of MECP2gene may be involved in autism.