SUPEROXIDE DISMUTASE 1 AND 2 GENE POLYMORPHISM IN TURKISH VITILIGO PATIENTS
Tuna A1, Ozturk G1, Gerceker TB1, Karaca E2,*, Onay H2, Guvenc SM2, Cogulu O2
*Corresponding Author: Emin Karaca, M.D., Associacte Professor, Department of Dermatology and Venerology, Faculty of Medicine, Ege University, Kazım Dirik mah, Izmir, Turkey. Tel: +90-232-3903961-+90-532-2579285. Fax: +90-232- 3903971. E-mail: karacaemin@gmail.com
page: 67

DISCUSSION

The SOD enzymes together with glutathione peroxidase and catalase play a critical role, assuring the cell protection against free radicals. These enzymes contain redox metals in the centers of their catalytic zones that transform superoxide radicals to hydrogen peroxide and oxygen [14-18]. Oxidative stress can trigger a reaction that causes melanocytes destruction. Thus, the lesions of vitiligo may be brought on by psychological stress or physical events. The trauma and stress cause a catecholamine release, which results in vasoconstriction and hypoxia. Following cellular hypoxia and reoxygenation there is an increase in free oxygen radicals and toxic materials. In a study on malondialdehyde (MDA), level, SOD and glutathione peroxidase activity in the tissues of 114 vitiligo patients, Yildirim et al. [10] found tissue SOD activity of the patients was significantly higher than the control group. It was considered that the increased SOD activity observed in that study was caused by a reactive increase against excessive superoxide anion production [10]. This is the first study to evaluate the relationship between the SOD1 and SOD2 polymorphisms and vitiligo. In terms of the SOD2 Ala-9Val (C/T), the TT genotype frequency in the patient group was statistically and significantly higher than the control group. We observed a 2-fold relative risk increase for the development of vitiligo in subjects with the TT genotype. Thus, while not conclusive, our results do suggest that the SOD2 polymorphism might play a role in vitiligo. In the literature, studies of the CuZn-SOD, described as the SOD1 enzyme, found the frequency of the Ala4Val mutation in SOD1 to be significantly higher than other mutations [5,19,20]. In our study, when we compared the distribution of genotype for the SOD1 35 A/C polymorphism, no significant diversity could be determined (p = 0.277). Likewise, when we compared groups, focusing on the SOD1 35 A/C polymorphism allele distribution, no significant diversity could be determined either (p = 0.214). The SOD1 enzyme is cytosolic, and the antioxidant reactions occur in the mitochondria. This might explain the similarity of genotype and allele frequencies in both the cohort and control group. The SOD2 enzyme, also known as Mn-SOD, has been studied more extensively than SOD1 due to the fact it is mitochondrial and inducible. The production of this particular enzyme rises via transcription in conjunction with a rise of the superoxide production. Two polymorphic structures have been determined for the SOD2 gene: Ala- 9Val polymorphisms that is the I1e58Thr polymorphism occurring in the 339th nucleotide via the transformation of C to T, and the Ala-9Val polymorphism that occurs in the 1183th nucleotide, again via the transformation of C to T. The Ile58Thr polymorphism reduces the enzymatic activity. The Ala/Val change occurs in the proteinís mitochondrial target series where it causes greater problems than those associated with the enzyme activity during the transfer of enzymes to the mitochondria [14]. Sutton et al. [21] showed that the SOD2 alanine amino acid in liver of rats is more active than the valine amino acid. In this study, results have indicated that the increase in TT homozygosity in vitiligo cases causes problems during the transfer of enzymes to the mitochondria. This is followed by a decrease in the SOD2s antioxidant effect. The Ala-9Val polymorphism has been studied in relation to Parkinsonís disease, schizophrenia, urolithiasis, adult-onset obesity, motor neuron disease, non familial idiopathic dilated cardiomyopathy, age-related macular degeneration, non alcoholic fatty liver disease, diabetic neuropathy, various cancers such as breast, prostate, stomach, colon, lung and skin cancer [22-29]. The SOD2 polymorphism, however, has been generally studied in relation to DM and its associated complications [29-32]. Previous studies have shown that different polymorphisms from various SOD isoforms can be associated with vitiligo. Additionally, there have also been studies evaluating the expression and enzyme activity of SOD isoforms, in both blood and tissue. Many of these studies have produced conflicting outcomes, especially concerning the peripheral blood samples of vitiligo patients. Picardo et al. [33] showed that blood levels of SOD were not significantly different in vitiligo patients, thus indicating that the melanocyte damage seen in vitiligo was not linked to generalized oxidative stress. In contrast, Laddha et al. [34] reported that increased activity of SOD2 and SOD3 due to polymorphisms may be genetic risk factors leading to susceptibility and progression of vitiligo. Hence, suggesting that the genetic make-up of an individual may form a basis for the effective treatment of the disease. In the studies related to SOD expression, both vitiliginous and non vitiliginous skin of patients showed a significant increase in the isoforms of SOD [35,36]. Because the same polymorphism could not be determined in all patients, the idea that the antioxidant system, in conjunction with various other pathways, plays a role in the diseaseís pathogenesis is well supported. One of the limitations of this study was our inability to exactly measure the enzyme activities of SOD1 and SOD2 genes. It would have been useful to highlight the effects of polymorphisms studied, and correlate the genotyping data. Consequently, this study needs to be substantiated by future studies containing larger patient numbers.



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