Haluk Akin

Association between Ala–9Val polymorphism of Mn-SOD gene and schizophrenia

Reactive oxygen species (ROS) have been suggested to play an important role in physiopathology of schizophrenia. The major intracellular antioxidant enzymes, copper-zinc superoxide dismutase in the cytoplasm and manganese superoxide dismutase (Mn-SOD) in the mitochondria, rapidly and specifically reduce superoxide radicals to hydrogen peroxide. Polymorphisms in the genes encoding antioxidant enzymes should therefore result in predisposition to schizophrenia. The present study was performed to assess whether there is a genetic association between a functional polymorphism (Ala-9Val) in the human Mn-SOD gene in schizophrenic patients (n=153) and healthy controls (n=196) using a PCR/RFLP method. Significant differences in the genotypic distribution between schizophrenics and controls were observed. Genotypic distribution with 14 (9.2%) Ala/Ala, 106 (69.3%) Ala/Val and 33 (21.6%) Val/Val subjects in schizophrenia was different from those of controls with 46 (23.5%), 83 (42.3%) and 67 (34.2%), respectively (p<0.0001). When the patients with schizophrenia were divided into the subgroups as disorganized, paranoid and residual, there was a significant difference in genotypic distribution among the subgroups (chi2=11.35, df=4, p=0.023). This association between -9Ala Mn-SOD allele and schizophrenia suggests that -9Ala variant may have a contribution in the physiopathogenesis of schizophrenia. Further investigations are warranted in larger populations with other susceptible genes that might be associated with schizophrenia.

Adenosine deaminase and xanthine oxidase activities in bladder washing fluid from patients with bladder cancer: a preliminary study

Activities of adenosine deaminase (AD), and xanthine oxidase (XO) enzymes were measured in bladder washing fluid (BWF) from 37 patients with bladder cancer. The patients were divided into several groups according to their sex; pattern, number, and depth of the tumors; and tumor grade. There was a statistically significant difference in XO activities between the patients having no tumor and papillary tumor (p < 0.002). The differences in XO values between the patients having no tumor and single tumor; and with no tumor and multiple tumors were statistically significant (p < 0.012, p < 0.016 respectively). XO activities were increased in patients with both papillary and multiple tumors compared to tumor-free group. Regarding to the depth of tumors, only the differences in XO values between the patients having no tumor and superficial tumor was statistically significant (p < 0.037). XO values of patients in grade1 were higher than the patients having no tumor (p < 0.010). AD activities in patients with multiple and invasive tumor were increased compared to patients with single and superficial tumor. AD values in grade 3 were lower than grade 2. However, we did not find any statistically significant differences in AD activities in all groups. As a conclusion, increased XO activity in BWF might be a potentially important finding as an additional diagnostic biochemical tool for bladder cancer. But we could not say this for AD activity. Further investigations in a larger cohort of patients with bladder cancer are needed to enlighten the possible diagnostic role of XO and AD in BWF.

Fragile X Syndrome and Cerebral Perfusion Abnormalities: Single-Photon Emission Computed Tomographic Study

Fragile X syndrome is an inherited disorder caused by a defective gene on the X chromosome. It is associated with developmental or behavioral symptoms and various degrees of mental retardation. Morphologic abnormalities and altered perfusion of various brain areas can underlie these functional disturbances. The aim of this study was to investigate the cerebral perfusion state in patients with fragile X syndrome using single-photon emission computed tomography (SPECT). Structural and functional assessment was also performed by magnetic resonance imaging (MRI) and electroencephalography (EEG). Eight boys with cytogenetically confirmed fragile X syndrome (mean age 8.8 ± 4.4 years, range 5–18 years), were included. All patients had mental retardation, with a mean IQ of 58.9 ± 8.8 (range 40–68), and additional neurobehavioral symptoms. SPECT revealed cerebral perfusion abnormalities in six patients (75%), most commonly in the frontoparietotemporal area and prominent in the right hemisphere. The SPECT and EEG findings were concordant: hypoperfused areas in SPECT corresponded to regions of persistent slow-wave paroxysms on EEG. On the other hand, cranial MRI was abnormal qualitatively only in two patients (25%) showing cerebellar and vermal hypoplasia and cerebral hemispheric asymmetry. Our results indicate that cerebral perfusion abnormalities, which are correlated with electrophysiologic findings but not necessarily with anatomic abnormalities, can underlie the pathogenesis of the clinical findings observed in fragile X syndrome.

Associations between Mn-SOD genetic polymorphism and schizophrenia

We read the comments of Dr. Pae about our recent study that was aimed to clarify the association between Mn-SOD genetic polymorphism and the different subgroups of schizophrenia. Additionally we extended our aim to seek the relation between the genetic polymorphism and presence of tardive dyskinesia. The contradictory studies that investigate the role of MnSOD genetic polymorphism in the etiology of schizophrenia and tardive dyskinesia (Hori et al., 2000; Zhang et al., 2002; Zhang et al., 2003) have been discussed in the manuscript by Akyol et al. (2005). As we indicated in the manuscript, there may be ethnic differences both in the genetic polymorphisms of Mn-SOD gene and also associations between polymorphism and schizophrenia and/or tardive dyskinesia. Therefore it may not be relevant to pool the data from different ethnic groups. On the other hand pooling the data increases the sample size and power of analysis. Due to the difficulties in providing large number of subjects, the use of insufficient number of samples is the major problem in this kind of association studies. Similarly data from Dr. Paes laboratory should also be interpreted with caution because of low number of sample size. Therefore further studies are warranted in different ethnic groups with larger populations. Another issue that Dr. Pae raised about our data is “deviation of the sample from Hardy Weinberg equilibrium”. We would like to emphasize that the expected frequencies of the genotypes according to HardyWeinberg equilibrium were within the range of 95% confidence interval of the observed genotypes. We agree with Dr. Pae that more polymorphic variants and sample should be included in further studies.