Involvement of superoxide dismutase isoenzymes and their genetic variants in progression of and higher susceptibility to vitiligo.

Oxidative stress has been implicated as the initial triggering event in vitiligo pathogenesis leading to melanocyte destruction. Here, we report a significant increase in oxidative stress in vitiligo patients as evidenced by high lipid peroxidation levels suggesting an imbalance in the antioxidant enzyme system as reported in our previous studies. This study examined the role of the enzymatic antioxidant SOD, which converts the pro-oxidant superoxide into H2O2, in vitiligo pathogenesis. The activity of three isoforms of SOD, i.e., SOD1, SOD2, and SOD3, was significantly higher in vitiligo patients. To identify the underlying mechanism for the increase in activities of SOD isoforms, we explored the SOD1, SOD2, and SOD3 genes for their genetic variations and transcript levels. The SOD2 Thr58Ile (rs35289490) and Leu84Phe (rs11575993) polymorphisms were significantly associated with vitiligo patients, and the Val16Ala (rs4880) polymorphism was associated with active vitiligo patients. Interestingly, SOD2 activity was contributed by these polymorphisms along with its increase in transcript levels in patients. SOD3 activity was associated with the Arg213Gly (rs8192291) polymorphism. The SOD3 transcript levels were also increased in patients, which might contribute to the increased SOD3 activity. However, we could not establish the genotype-phenotype correlation for SOD1 as we could not detect any novel or reported SNPs in SOD1. In addition, both transcript and protein levels of SOD1 were unchanged between patients and controls, though SOD1 activity was increased in patients. Activities of SOD isoforms also correlated with progression of the disease as the activity was higher in active cases of vitiligo compared to stable cases. Here, we report that SOD2 and SOD3 polymorphisms may be genetic risk factors for susceptibility and progression of vitiligo and hence the genetic makeup of an individual may form a basis for the effective treatment of the disease. Overall, our results suggest that increased activity of SOD isoforms under the influence of genetic factors may lead to accumulation of H2O2 in cytoplasmic, mitochondrial, and extracellular compartments resulting in oxidative damage to the melanocytes.