| Introduction:Vitiligo is a common chronic depigmented skin disorder which caused by regional melanocytes depletion. The pathomechanism of vitiligo has still not been completely clarified, various possible pathomechanisms have been proposed, including the immune-mediated, the auto-cytotoxic/metabolic, the genetic factors and the neural dysfunction. But none of them can explain the pathomechanism of vitiligo perfectly. Recently, vitiligo is thought to be a polygenic hereditary disease, which is correlated with heredity and environment. Single nucleotide polymorphism (SNP) is an important factor for deciding the susceptivity of human diseases (especially multigenic diseases).It can be a good method, especially satisfies the demand of high precision for disease related gene positioning study of hereditary disorders.Inducible nitric oxide synthase (iNOS) is one of three key enzymes generating nitric oxide (NO) from the amino acid L-arginine. INOS derived NO plays an important role in numerous physiological and pathophysiological, including a role in neurotransmission, smooth muscle relaxation, and the response to immunogens. NO, an intercellular messenger, is also reported as a cytotoxic molecule involved in the development of autoallergic disease. NO's generation is regulated by multi-cytokines. Many researchers supposed that NO could regulate the self-destroy of melanocyte and the autoimmunity to participate in the development and progression of vitiligo.Objective: To investigate the associations between the polymorphisms of iNOS genes and risk of vitiligo in Chinese populations.Methods: In a hospital-based case-control study of 749 patients with vitiligo and 763 vitiligo-free controls was made in frequency according to the age and sex. Three polymorphisms of iNOS gene were genotyped by using the PCR -RFLP and MS-PCR technique.Results: We found that an increased risk of vitiligo was associated with the iNOS-954GC (adjusted OR, 1.35; 95% CI, 1.00-1.81) genotype, compared with the -954GG genotype. Consistently we found that a high risk of vitiligo was associated with the iNOS-954 combined genotype GC+CC (adjusted OR, 1.36; 95% CI, 1.02-1.81), compared with the -954GG genotype.From the clinical types analysis we found that this high risk association was observed in the subjects with vulgaris vitiligo (adjusted OR=1.36, 95% CI=1.01-1.82) , active vitiligo (adjusted OR=1.35, 95% CI=1.00-1.82) and vitiligo without other autoimmune diseases (adjusted OR=1.38, 95% CI=1.04-1.85) but not found in patients with sex,onset and with/without family history.We didn't find iNOS-1173 and E16+14 polymorphism in all the case and control subjects by PCR-RFLP technique and MS-PCR technique. We also didn't find the risk association from the clinical types'analysis. Furthermore, in the haplotype analysis of three polymorphisms of iNOS gene, we found that the CCC haplotype genotypes were associated with an increased risk of vitiligo.Besides, the serum iNOS activity (19.56±6.55 U /ml) was significantly higher in patients than in controls (12.82±3.35 U /ml)(P<0.05), and it is associated with iNOS-954 combined genotype GC+CC.In conclusion: iNOS gene polymorphism may play an important role in the genetic susceptibility to the severity and development of vitiligo. When the patients were classified by the clinical groups, genotype frequencies between patients and control showed significantly different, and the distributions of iNOS polymorphism were various since region, race and heredity background difference. It was the first observation of iNOS gene polymorphism associated with the pathogenesis of vitiligo in the northwest of china; iNOS gene may also be a marker to estimate the clinical stage and prognosis of the vitiligo. |
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