The Polymorphism Of Mitochondrial DNA And Association Between Mitochondrial DNA And Schizophrenia

Objective: There are few studies detecting on the polymorphisms of mitochondrial DNA hypervariable region and four SNPs(C5178A,A10398 G,G13708A and C13928G)in coding region of the northern Han population.Moreover,associations between mt DNA and schizophrenia are controversial.This study characterized the genetic variations of mitochondrial DNA(mt DNA)to elucidate the maternal genetic structure of the northern Chinese Han and to detect the association between mt DNA and schizophrenia.Methods: 313 patients with schizophrenia and 326 unaffected participants of the northern Chinese Han population were included in a prospective study.Single-nucleotide polymorphisms(SNPs)including C5178 A,A10398G,G13708 A,and C13928 G,were analyzed by polymerase chain reaction–restriction fragment length polymorphism(PCR–RFLP).Hypervariable regions I and II(HVSI and HVSII)were analyzed by sequencing.Results: 313 patients in the patient group and 326 unaffected participants in the control group were analyzed for association study.The frequency of haplogroup M8 a significantly differed between groups(P = 0.019,OR = 0.315 [0.114-0.869]).Among females,a statistically significant difference was detected in the frequency of haplogroup A between the 2 groups(P = 0.043,OR = 0.465 [0.219-0.989]).The frequencies of haplogroups M7 and N9 were significantly different between male patients with schizophrenia and unaffected male participants(P = 0.028,OR = 3.074 [1.080-8.749];P = 0.040,OR = 0.348 [0.122-0.990],respectively).However,the significance could not survive the Bonferroni correction.The results showed that the 4 SNPs and 11 haplotypes,composed of the 4 SNPs,did not differ significantly between patient and control groups.No significant association between haplogroups and the risk of schizophrenia was ascertained after Bonferroni correction.326 unrelated individuals in control group were included in the study of maternal genetic structure.The results indicated a high gene diversity value(0.9997 ± 0.0003),a high polymorphism information content(0.99668)and a random match probability(0.00332).These samples were classified into 312 haplotypes based on polymorphism of hypervariable regions and 4 SNPs,with 11 shared haplotypes.The most common haplogroup was D(20.25%),followed by B(14.42%),M8(12.27%),A(11.66%),R9(11.04%),N9(7.67%),and M9(5.83%).The minimum allele frequencies of C5178 A,A10398G,G13708 A,and C13928 G were 0.255,0.472,0.058,and 0.123,respectively.Conclusion: There was no evidence of an association between mt DNA(the 4 SNPs and the control region)and schizophrenia in the northern Chinese Han population.Drawing a conclusion,the results expand the available knowledge of human genetic diversity.The characteristics of Liaoning Han can be used for personal identification and to estimate geographic origin in forensic cases.