By testing additional loci that showed suggestive association in the genome-wide study, using two replication cohorts of European descent, we observed replicated association of generalized vitiligo with variants at 3p13 encompassing FOXP1 (rs17008723, combined P=1.04x10(-8)) and with variants at 6q27 encompassing CCR6 (rs6902119, combined P=3.94x10(-7)).
We also detected associations between generalized vitiligo and SNPs in two additional immune-related loci, RERE (P=7.07x10(-15)) and GZMB (P=3.44x10(-8)), and in a locus containing TYR (P=1.60x10(-18)), encoding tyrosinase.
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.
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.
We identified a quantitative trait locus for vitiligo age of onset in the major histocompatibility complex (MHC) class II region, located near c6orf10-BTNL2 (rs7758128; P=8.14 × 10(-11)), a region that is also associated with generalized vitiligo susceptibility.
We identified a quantitative trait locus for vitiligo age of onset in the major histocompatibility complex (MHC) class II region, located near c6orf10-BTNL2 (rs7758128; P=8.14 × 10(-11)), a region that is also associated with generalized vitiligo susceptibility.
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.
Moreover, the increased IFN-γ levels in patients lead to increased ICAM1 expression, which could be a probable link between cytokines and T-cell involvement in pathogenesis of GV.
Moreover, the increased IFN-γ levels in patients lead to increased ICAM1 expression, which could be a probable link between cytokines and T-cell involvement in pathogenesis of GV.
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.
The alleles HLA-A*32 (P = 0.0156, Pc = 0.3120, OR = 22.43, 95% CI = 1.12-449.46) and HLA-DQB1*06 (P = 0.0207, Pc = 0.1035, OR = 0.28, 95% CI = 0.10-0.81) were associated with both localized and generalized vitiligo.
The alleles HLA-A*32 (P = 0.0156, Pc = 0.3120, OR = 22.43, 95% CI = 1.12-449.46) and HLA-DQB1*06 (P = 0.0207, Pc = 0.1035, OR = 0.28, 95% CI = 0.10-0.81) were associated with both localized and generalized vitiligo.
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.