Correlation Analysis Of Polymorphisms In MtDNA 3243, 3316, 3394 Point Mutation With Schizophrenia

Background and ObjectSchizophrenia (SZ) is the most common syndrome in psychotic disease. There are 80%～90% SZ patients in psychotic hospital occupied the fast position. The etiology of SZ is not very clear. It may arise from interactions between environmental and genetic factors.Genetic factors play more important role, in general.Mitochondron is one of the important organs in eukaryotic cells. Energy conversion and oxidative phosphorylation are mainly performed in the mitochondria. Mitochondrial DNA(mtDNA) has not repair system and is directly exposed to hyperoxia during oxidative phosphorylation; it alsao lacks of the histone pretection like the nuclear genome, therefore, mtDNA is easier to be affected by oxidative damage and to be repaired is difficulter and its degree of injury and mutation rate is markedly higher compared to the nuclear DNA. Many mtDNA mutations have been identified in schizophrenia and various diseases such as diabetes mellitus.In order to study the relations of genetic risk factors with SZ in the Henan Han population, we adopted PCR-RFLP to study whether the mtDNA gene at nucleotide 3243,3316,3394 point mutation are associated with risk of SZ in the Henan Han population.MethodsAll SZ cases must to be corformed with the standard of DSM-IV and CCMD-3 of the diagnostic criteria,250 cases as patient group with schizophrenia (138 men and 112 women).292 unrelated healthy controls were selected from subjects in outpatient department who underwent regular check-up examinarion (160 men and 132 women). All people are Henan Han Chinese and without epilepsy, cancer and hepatic or renal diseases.3～5ml peripheral venous blood samples were collected.Genomic DNA was extracted from white cells.Using the primers, we performed polymerase chain reaction amplification and refined frequence length polymorphism(PCR-RFLP). These products were electrophoresed on 2.5% agarose gels, and DNA was visualized by ethidium bromide straining.Genotype was estimated by the gene-counting method. All statistical analyses were performed with SPSS 17.0 software. Categorical Parameters were summarized as number (%), and compared with chi-square(χ-)-test. The relative risk of genotypes was described by odds ratios (OR) and 95% confidence intervals (95%CI) and test standard a=0.05.Results1. In Henan Han population, there are evident differences of mtDNA3394 alleles frequency between SZ group and control group (P=0.007, OR= 4.596,95%CI: 1.505～14.033).The sex difference analasis shows that there is a high frequency in male SZ group and there is evident difference in male group (P=0.034, OR= 5.581,95%CI:1.185～26.287),but we can't find obvious differences between female patiants and the control group (P=0.177, OR=3.765,95%CI:0.744～19.048).2. In Henan Han population, we can't find obvious differences of mtDNA3316 between SZ group and control group (P=0.138, OR=0.314,95%CI:0.082～1.197).The sex difference analasis shows that there is evident difference in male group (P=0.033, OR=0.962,95%CI:0.927～0.999), but we can't find obvious differences between female patiants and the control group (P=1.0, OR=1.164, 95% CI:0.161～8.398k)3. We did not find case of point mutation in mtDNA3243 after we had researched all casese of two groups. There is no difference between SZ group and control group.4. In Henan Han population, we can't find differences of combined gene mutation between SZ group and control group P=0.461.Conclusion1. Point mutation in mtDNA3394 and mtDNA3316 may be the risk factor of SZ generous for males.2. The mutation of mtDNA3243 sit may not have association with SZ generation.