The Mapping Study Of Susceptibility Gene For Schizophrenia In Shandong Province

Schizophrenia,(SZ) is a severe mental disorder characterized by hallucinations,delusions, flat affect, and cognitive impairment. The prevalence of schizophrenia in Chinaand worldwide are5.31‰, and6.55‰respectively. The etiology of SZ is not clear yet.Biological, psychological and social factors play important role together in thepathogenesis of schizophrenia. Family, twin and adoption studies all provide strongsupport for genetic factors in the etiology and pathogenesis of this disorder. However,the genetic mechanism of schizophrenia is complex, multiple genes of modest or smalleffect and rare deleterious variants with large effect are both likely in schizophreniapredisposition. Over the last two decades，a number of chromosomal regions and severalpromising candidate genes have been identified by linkage and association studies.The relationship between the association of the genetic variation in the5,10-methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders areinconsistent and inconclusive. MTHFR is located at1p36.3of chromosome1and isinvolved in the one-carbon metabolic pathway which is essential for DNA biosynthesis andthe epigenetic process of DNA methylation. Several lines of evidence have suggested thattwo functional polymorphisms, of the methylenetetrahydrofolate reductase gene (MTHFR)C677T and A1298C, may be implicated in the etiology of schizophrenia.ObjectiveStudy the association between the MTHFR gene and schizophreniaMethods Stage1：Genomewide association study of981schizophrenic patients in ShandongProvince of ChinaA total of981schizophrenic cases were recruited from Shandong Mental HealthCenter. The average age of the cases was33.80±11.98and the average age of onset was26.04±9.72. The male/female ratio was0.99：1(489/492). A total of1000healthycontrols(controls) were blood donors from the Blood Center of Shandong Province. Theaverage age of the controls was23.08±5.67, and the male/female ratio was1.32：1(569/431). The controls were not screened for mental illness. Genomic DNA was extractedand two DNA pools from981cases and1000controls were constructed respectively byadding up10ul of each sample. A total of400microsatellite markers (ABI Prism linkagemapping set version2.5) spaced approximately10cM interval from human genome wereused for genotyping of two separated DNA pooling samples. Statistic analysis was carriedout by Chi-square method with CLUMP software to compare the difference of allelefrequency of each locus between the two pooling samples.Stage2：Genotyping of SNPs in MTHFR by High Resolution Melting (HRM)ResultsThe data analysis of the two DNA pooling samples genotyped by400microsatellitemarkers (ABI Prism linkage mapping set version2.5) revealed that significant statisticdifference in allele frequency was found at D1S450between cases and controls, and the P-value was＜0.0001. This marker is near MTHFR gene. Therefore，studies are warranted toshed further light on these relationships.We encountered technical problem in the genotyping of SNPs of MTHFR genewith HRM technology, so that we did not obtain the data of these SNPs, further studyneeds to be carried out for this in the future.Conclusions：Chromosome1is the largest human chromosome. Among all23pairs,2834genes are discovered on it. A lot of genetic loci and genes associated with schizophrenia are reportedon this chromosome. D1S450is located on1p36and the result of our stage1resultindicated that it was associated with schizophrenia. Based on these finding，a nearby geneMTHFR was selected as a candidate gene for the further study.Unfortunately, we did notobtain the expected data from the SNPs genotyped due to technical problems.