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.
Frequency of COX2-1195 AA, AG, GG genotypes showed no significant association among patients with vitiligo (P = 0.626, 0.321, 0.08, respectively); those with generalized vitiligo (P = 0.739, 0.291, 0.101, respectively) and those with segmental vitiligo (P = 0.410, 1.00, 0.676, respectively) compared to the control group.
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.
Collectively, C allele at the TSLP -847C>T polymorphism may increase susceptibility to generalized vitiligo through decreasing TSLP mRNA expression levels.
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.
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)).
This study showed a significant trend towards an association with the combination of the GSTM1/GSTT1 double null polymorphism and generalized vitiligo.
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.
These results implicate PTPN22 in mediating susceptibility to generalized vitiligo and associated autoimmune diseases, but do not support a role for CTLA4.
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.
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.
The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo.
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.
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.
IL-2 was significantly raised (P = .028) in localized vitiligo, whereas IL-17 and IL-22 were significantly raised in generalized vitiligo (P = .00 and P = .019, respectively).
IL-2 was significantly raised (P = .028) in localized vitiligo, whereas IL-17 and IL-22 were significantly raised in generalized vitiligo (P = .00 and P = .019, respectively).
To assess the serum levels of cytokines secreted by Th1 (IL-2, TNF-α), Th2 (IL-6), and Th17 cells (IL-17, IL-22) in patients with localized vitiligo and generalized vitiligo and to correlate their levels with the extent, duration, and activity of disease.