Association between the MnSOD Ala-9Val polymorphism and development of schizophrenia and abnormal involuntary movements in the Xhosa population |
| |
| Authors: | Hitzeroth Angelika Niehaus Dana J H Koen Liezl Botes Willem C Deleuze J F Warnich Louise |
| |
| Affiliation: | Department of Genetics, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. ahitz@sun.ac.za |
| |
| Abstract: | Reactive oxygen species (ROS)-mediated damage has been hypothesized to play a role in the development and poor outcome of schizophrenia, as well as the development of neuroleptic-induced abnormal involuntary movements. Recently, the functional polymorphism (Ala-9Val) in the manganese superoxide dismutase (MnSOD) gene (part of the antioxidant defense mechanism) was found to be associated with schizophrenia in a Turkish population. This study was aimed at replicating this finding in a Xhosa population. In addition, the role of Ala-9Val in abnormal involuntary movement and tardive dyskinesia development in the Xhosa population was also investigated. The schizophrenic patient group (n=286) and a healthy control group (n=243) were genotyped for the Ala-9Val polymorphism using heteroduplex-single stranded conformational polymorphism (HEX-SSCP) analysis. No significant difference in genotype or allele frequency could be observed between the schizophrenia and control group (P=0.294 and P=0.528 respectively). In addition no association could be found between the polymorphism and symptom severity (SANS and SAPS). The Xhosa schizophrenia patient group with abnormal involuntary movements (n=54) and a subgroup with tardive dyskinesia (n=30) was found to significantly differ in Ala-9Val genotype frequency (P=0.008 and P=0.011 respectively) compared to the Xhosa schizophrenia patient group without abnormal involuntary movements (n=204). However, no significant difference was found for the allele frequencies (P=0.955 and P=0.161). Further, using ANCOVA no association was found between AIMS score and genotype in the group with abnormal involuntary movements (P=0.1234). However, in the patient group with tardive dyskinesia an association was observed between genotype and AIMS score (P=0.0365). These results do not support a major role of the MnSOD Ala-9Val polymorphism in the development of schizophrenia or symptom severity in the Xhosa population. Yet it seems to be involved in the development of abnormal involuntary movements and tardive dyskinesia and may even modulate the severity of tardive dyskinesia. |
| |
| Keywords: | ·OH, hydroxyl radical A, adenine AIM, abnormal involuntary movements AIM−, without abnormal involuntary movements AIM+, with abnormal involuntary movements AIMS, abnormal involuntary movement scale Ala, alanine ANCOVA, analysis of covariance BHPR, Bunney–Hamburg Psychosis Rating bp, basepairs BPRS, Brief Psychiatric Rating Scale C, cytosine CAT, catalase CNS, central nervous system DIGS, Diagnostic Interview for Genetic Studies DNA, deoxyribonucleic acid dNTP, deoxynucleoside triphosphate DRD3, dopamine D3 receptor DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, fourth edition G, guanine Gly, glycine GSHPx, glutathione peroxidase H2O2, hydrogen peroxide HEX-SSCP, heteroduplex-single strand conformational polymorphism HWE, Hardy–Weinberg equilibrium MgCl2, magnesium chloride MnSOD, manganese superoxide dismutase MTS, mitochondrial targetting sequence n, number NH4, ammonium O2−, superoxide radical PANSS, Positive and Negative Syndrome Scale PCR, polymerase chain reaction PUFAs, polyunsaturated fatty acids ROS, reactive oxygen species SANS, Scale for the Assessment of Negative Symptoms SAPS, Scale for the Assessment of Positive Symptoms Ser, serine SOD, superoxide dismutase SPSS, Statistical Package for the Social Sciences T, thymine TBARS, thiobarbituric acid reactive substances TD, tardive dyskinesia TD+, tardive dyskinesia positive TFPGA, Tools for Population Genetic Analysis UV, ultraviolet Val, valine. |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
