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
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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 protein’s 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 Parkinson’s 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 disease’s 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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