Association Study Of Four Single Neuclear Polymorphisms In MECP2 Gene With Child And Adolescent-onset Schizophrenia, And Comparison On MECP2 Gene Polymorphisms Between Child And Adolescent-onset Schizophrenia And Pervasive Developmental Disorders

Objectives:1. Probe into the differences of child and adolescent-onset schizophrenics and normal people on 4 single nucleotide polymorphisms (SNPs) (rs2734647, rs2239464, rs2071569, and rs61748381) of MECP2;2. Investigate whether there are differences in genetic polymorphism of child and adolescent-onset schizophrenia and pervasive developmental disorder in 4 SNPs (rs2734647, rs2239464, rs2071569, and rs61748381) of MECP2.Methods:Venous blood were taken from 85 cases of Han nationality patients with child and adolescent-onset schizophrenia (onset before 17 years old, hereinafter referred to as child and adolescent-onset group) who meet the diagnostic criteria in both the International Classification of Diseases-10th Revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV),80 cases of Han nationality patients with Pervasive Developmental Disorders (PDDs) s (hereinafter referred to as PDDs group) who meet the DSM-IV diagnostic criteria for PDDs, and 89 cases of normal people (control group). Taqman assay was adopted in genotyping of SNPs on 4 locus of MeCP2 gene (rs2734647, rs2239464, rs2071569, and rs61748381).Results:1. Comparisons of child and adolescent-onset schizophrenia and control group(1) rs2734647:The proportion of T/C genotype of patients from child and adolescent-onset group is higher than that of the control group, while the proportions of T/T and C/C are lower than that of the control group (P<0.05). In child - onset group (schizophrenics whose onset age is not more than 13), the proportion of T/C genotype is higher than that of the control group, while the proportions of T/T and C/C are lower than that of the control group (P<0.05). In adolescent-onset group (schizophrenics whose onset age is from14 to 17), the proportion of T/C genotype is higher than that of the control group, while the proportions of T/T and C/C are lower than that of the control group (P<0.05). In addition, the proportion of T/C genotype of the child-onset group is higher than that of the adolescent-onset group (P<0.05). Besides, the T allele frequency of child-onset group is higher than that of the adolescent-onset group, while the C allele frequency of child-onset group is lower than that of the adolescent-onset group (P<0.05).(2) rs2239464:The proportion of A/G genotype of patients from child and adolescent-onset group is higher than that of the control group, while the proportions of A/A and G/G are lower than that of the control group (P<0.05). In child-onset group, the proportion of A/G genotype is higher than that of the control group, while the proportions of A/A and G/G are lower than that of the control group (P<0.05). In adolescent-onset group, the proportion of A/G genotype is higher than that of the control group, while the proportions of A/A and G/G are lower than that of the control group (P<0.05).(3) There were strong Linkage Disequilibrium among rs2734647、rs2239464、 rs2071569 and rs61748381 in child and adolescent-onset schizophrenia patients. T G G C haplotype constructed by 4 genetic loci were more common in control group compared to child and adolescent-onset schizophrenia(P<0.05).2. Comparisons of child and adolescent-onset schizophrenia and pervasive developmental disorder(1) rs2734647:The proportion of genotype T/C in child and adolescent-onset group is higher than PDDs group, while proportions of genotype T/T and C/C are lower than PDDs group (P<0.05); The proportion of genotype T/C in child-onset group is higher than PDDs group, while proportions of genotype T/T and C/C are lower than PDDs group (P<0.05); the allele frequency of T in child-onset group is higher than PDDs group, but the allele frequency of C is lower than PDDs group (P<0.05). The proportion of genotype T/C in adolescent-onset group is higher than PDDs group, while proportions of genotype T/T and C/C are lower than PDDs group (P<0.05).(2) rs2239464:The proportion of genotype A/G in child and adolescent-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05); The proportion of genotype A/G in child-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05); the allele frequency of A in child-onset group is higher than PDDs group, but the allele frequency of G is lower than PDDs group (P<0.05). The proportion of genotype A/G in adolescent-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05).(3) rs2071569:The proportion of genotype A/G in child and adolescent-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05); The proportion of genotype A/G in child-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05); the allele frequency of A in child-onset group is higher than PDDs group, but the allele frequency of G is lower than PDDs group (P<0.05). The proportion of genotype A/G in adolescent-onset group is higher than PDDs group, while proportions of genotype A/A and G/G are lower than PDDs group (P<0.05).(4)C G G C haplotype constructed by 4 genetic loci were more common in child-onset group compared to PDDs group(P<0.05), while the frequency of T T G C haplotype is lower than that of PDDs group(P<0.05).Conclusions:1. MECP2 gene may be a susceptibility gene for child and adolescent-onset schizophrenias in Han Chinese patients of Yunnan Province.In addition, compared to adolescent-onset schizophrenics, this type of genetic susceptibility is more obvious in child-onset schizophrenics.2. There were strong Linkage Disequilibrium among rs2734647、rs2239464、 rs2071569 and rs61748381 on MECP2 gene in child and adolescnet-onset schizophrenia.In addition, T G G C haplotype constructed by 4 genetic locimight bea resistant locus for child-onset schizophrenia.3. Differences exist in gene polymorphisms of rs2734647, rs2239464, and rs2071569 between child and adolescent-schizophrenia and pervasive developmental disorderindicate that genetic susceptibility in MECP2 gene of thesetwo diseases might be different.