Then the NOS activity and NO production were increased. Our result certified iNOS-954 C allele can increase iNOS activity. To the best of our knowledge, this is the first study on the association between the iNOS polymorphisms and vitiligo in the Han Chinese population. An early event in the onset of vitiligo appears to involve the overproduction of tetrahydrobiopterin, which leads to the accumulation of a potent inhibitor of melanin biosynthesis. The synthesis of tetrahydrobiopterin is cytokine induced and it is an essential cofactor in the enzymatic activity of iNOS. LPS/cytokines can stimulate normal human melanocytes express iNOS. This enzyme might therefore be involved in the altered melanin production associated with post-inflammatory hypopigmentation. In vitiligo, the increase of iNOS activity caused by overexpression of the tetrahydrobiopterin or LPS/ cytokines can produce plenty of NO generation. NO has been reported to contribute to the loss of melanocytes in vitiligo by reducing de novo attachment of melanocytes to the extracellular matrix components. Moreover, increased iNOS activity induces NO production and O2 2, which result in the accumulation of hydrogen peroxide. High of hydrogen peroxide can lead to melanocytes destruct and depigmentation ultimately. The increased NOS activity had been confirmed in vitiligo affected/ nonaffected melanocytes and keranocytes. Our study also confirmed that the increased iNOS activity was related with the onset of vitiligo indirectly. However, the specific mechanisms of iNOS involved in the pathogenesis of vitiligo still need further research. In summary, we provide evidence that iNOS polymorphisms may influence the risk and clinical progression of vitiligo in Han Chinese populations. A statistically significantly increased risk of vitiligo was associated with the iNOS-954 genotype compared with the -954 GG genotype, which was more pronounced among vitiligo patients with the following characteristics: non-segmental, active vitiligo and without other autoimmune diseases. But no evident risk was associated with the iNOS1173 and Ex16+14 polymorphisms. Furthermore, we found the serum iNOS activity was significantly higher in vitiligo and was increased in iNOS-954 combined genotype compared with -954 GG genotype. Nevertheless, better-designed and larger prospective studies are needed to confirm these findings, and more detailed environmental exposure data are necessary to further test potential gene-environment interactions. The function of the vertebrate erythrocyte is agreed to be oxygen-transport by respiratory globin pigments. Across nonMLN4924 mammalian vertebrates, nucleated erythrocytes are present in the circulation often with extended longevity throughout the life cycle of the organism. Intriguingly, the potential contribution of nucleated erythrocytes as transcriptionally-active cells to nonrespiratory physiological processes has not been systematically addressed in non-mammalian species. Instead, red blood cell functions in non-mammalian vertebrates have tacitly been assumed to follow a highly conserved role as observed in mammalian anucleated erythrocytes. The immune response is understood to have a modular structure mainly formed by sub-sets of activated leukocytes responding to different combinations of PAMPs via PRRmediated recognition.