Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies (GWAS) of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes.
We previously reported the linkage signals on chromosomes 1, 7, and 17 in Caucasian families with generalized vitiligo and associated autoimmune diseases and identified the risk loci of chromosomes 17 and 1 as NLRP1 (NALP1) and FOXD3, respectively.
Our results provide evidence that the PTPN22 1858T allele contributes to risk of generalized vitiligo in European Caucasian populations, and underscores the importance of a genetically mediated autoimmune mechanism in the pathogenesis of vitiligo.
In addition, we analyzed five other family members out of three generations for the AIRE gene mutation and for polymorphisms in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene region and lymphoid protein tyrosine phosphatase (PTPN22) gene, which are associated with the occurrence of sporadic autoimmune Addison's disease, type 1 diabetes mellitus, and generalized vitiligo.
These results implicate PTPN22 in mediating susceptibility to generalized vitiligo and associated autoimmune diseases, but do not support a role for CTLA4.
The discovery that a single-nucleotide polymorphism (SNP) in lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, is associated with type 1 diabetes (T1D) has now been verified by numerous studies and has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis (JRA), systemic lupus erythematosus, Graves' disease, generalized vitiligo and other human autoimmune diseases.
The objective of this study was to ascertain if the disease-associated 1858T allele was also associated with generalised (nonsegmental) vitiligo and so the frequencies of the PTPN221858C/T alleles were investigated in 165 English patients with generalised vitiligo and 304 ethnically matched control subjects.
Later, genome-wide linkage studies of multiplex GV families identified NLRP1 and XBP1, which appear to be valid GV susceptibility genes that control key aspects of immune regulation.
Subsequent genomewide linkage studies identified NLRP1 and XBP1, apparent true GV susceptibility genes involved in immune regulation, and recent genome-wide association studies (GWAS) of GV in Caucasian and Chinese populations have yielded a large number of additional validated GV susceptibility genes.
Association of GV with CTLA4 (rs12992492, P=5.9E-05, OR=1.20; meta-P for rs231775=1.0E-04) seems to be secondary to epidemiological association with other concomitant autoimmune diseases.
In addition, we analyzed five other family members out of three generations for the AIRE gene mutation and for polymorphisms in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene region and lymphoid protein tyrosine phosphatase (PTPN22) gene, which are associated with the occurrence of sporadic autoimmune Addison's disease, type 1 diabetes mellitus, and generalized vitiligo.
Examination of five SNPs in the CTLA4 gene (rs1863800, rs231775, rs3087243, rs11571302, rs11571297, rs10932037) in the same 126 families yielded no evidence of allelic or genotypic association with either generalized vitiligo or the expanded autoimmune phenotype.
Narrow-band UVB (NB-UVB) treatment of vitiligo might act through its effects on vitamin D and its receptor.This study is the first to elucidate NB-UVB effects on immunohistochemical vitamin D receptor (VDR) expression in generalized vitiligo and correlate it with serum vitamin D and repigmentation response.
CAT-89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo, whereas no association was observed for -262G/A and exon polymorphisms.
In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population.
In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population.
We found that compared to the COMT-158 GG genotype, the COMT-158 GA genotype (adjusted odds ratio [OR], 1.39; 95% confidence interval [CI], 1.13-1.72) and the combined GA + AA genotype (adjusted OR, 1.41; 95% CI, 1.15-1.74) were associated with an increased risk of generalized vitiligo.