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Psoriasis vulgaris is a chronic inflammatory skin disease associated with complex genetic susceptibility. Recently, we identified a single-nucleotide variant rs1020760 at NFKB1 significantly associated with psoriasis in a Han Chinese population in deep analysis of exome and targeted sequencing ( P = 1.76 × 10−8). To investigate the potential association between rs1020760 and phenotypes of psoriasis vulgaris, we performed a genotype-phenotype analysis. A total of 9946 cases and 9906 controls with detailed clinical and demographic information were involved in this study, while the genotype data of rs1020760 was available in the previous targeted sequencing study of psoriasis. Genotype-based association testing revealed the additive model might provide the best fit for rs1020760 ( P = 5.44 × 10−8). Case-only analysis showed that the distribution of allele G was significantly different between the cases with and without family history ( Pallele = 4.07 × 10−3, Pgenotype = 5.75 × 10−3). The differences in allele and genotype frequencies were observed between all the subphenotypes and controls except for the genotype frequency of the late onset subgroup, while no difference was found in case-only analysis for the other two subphenotypes. Rs1020760 was preferentially associated with family history of psoriasis, implying that NFKB1 might not only play important roles in the development of psoriasis, but might also contribute to the special phenotypes of this disease. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic inflammatory skin disease and is affected by environmental and genetic factors. Gene-gene/environment interactions are strongly believed to contribute to the genetic risk of common diseases. A number of gene-environment interactions of atopic dermatitis were performed. However, there are few comprehensive investigations on the gene-gene (or genetic variants) interactions for atopic dermatitis. We explored the association model of 6 single nucleotide polymorphisms (SNPs) which were most significant ( P < 10E-05) in our previous genome wide association study (GWAS) for atopic dermatitis, and search for the possible genetic variant interactions based on the previous GWAS data using Generalized Multifactor Dimensionality Reduction and Plink 1.07 in the combined sample of 4,636 cases and 13,559 controls. The most significant associated evidence was observed under dominant model for SNPs rs3126085, rs12085366, and rs7701890, recessive model for SNP rs17173197, and additive model for SNPs rs2393903 and rs6010620. Three significant pair-way interactions were observed, including PRKAG2 and FLG SNPs (rs17173197 × rs3126085, P = 1.11E-15), PRKAG2 and TMEM232- SLC25A46 SNPs (rs17173197 × rs7701890, P = 2.22E-15), PRKAG2 and TNFRSF6B- ZGPAT SNPs (rs17173197 × rs6010620, P = 6.66E-16). Besides, a three-way significant interaction among PRKAG2, TMEM232- SLC25A46 and TNFRSF6B- ZGPAT SNPs (rs17173197 × rs7701890 × rs6010620, P = 5.99E-15) was observed in this study. These four genetic variant interactions confer susceptibility to atopic dermatitis, and highlight the genetic variant interactions in the etiology of atopic dermatitis in Chinese Han population. [ABSTRACT FROM AUTHOR]

Generalized vitiligo is an autoimmune disease characterized by melanocyte loss, which results in patchy depigmentation of skin and hair, and is associated with an elevated risk of other immune-related diseases. However, there is no reported study on the associations between immune susceptibility polymorphisms and the risk of vitiligo with immune-related diseases. The aim of this study was to evaluate the potential influence of 10 single-nucleotide polymorphisms (SNPs) at 18q21.31 (rs10503019), 4p16.1 (rs11940117), 3q28 (rs1464510), 14q12 (rs2273844), 12q13.2 (rs2456973), 16q12.2 (rs3213758), 10q25.3 (rs4353229), 3q13.33 (rs59374417), and 10p15.1 (rs706779 and rs7090530) on vitiligo with immune-related diseases in the Chinese Han population. All SNPs were genotyped in 552 patients with vitiligo-associated immune-related diseases and 1656 controls using the Sequenom MassArray system. Data were analyzed with PLINK 1.07 software. The C allele of rs2456973 at 12q13.2 was observed to be significantly associated with vitiligo-associated immune-related diseases (autoimmune diseases and allergic diseases) ( P = 0.0028, odds ratio (OR) = 1.27). In subphenotype analysis, the rs2456973 C allele was also significantly associated with early-onset vitiligo by comparing with controls ( P = 0.0001) and in the case-only analysis (P = 0.0114). We confirmed that 12q13.2 was an important candidate locus for vitiligo with immune-related diseases (autoimmune diseases and allergic diseases) and affected disease phenotypes with early onset. [ABSTRACT FROM AUTHOR]

Background Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases. Associations of genes, especially human leukocyte antigen (HLA)-DQ alleles, with BP indicate that genetic predisposition contributes to the disease. Objectives To evaluate the association of HLA class I and HLA class II alleles with susceptibility to BP in the northern Chinese Han population. Methods We performed genotype for HLA-A, -B, -C, -G, -DPA1, -DPB1, -DQA1, -DQB1 and -DRB1 loci in 105 patients with BP by Sanger sequence-based typing (SBT) method. These data were compared with a local control cohort of 420 age- and sex-matched cases. Results Among the HLA alleles described herein, the susceptibility alleles associated with a high prevalence of BP were A*11:01 (OR = 1.9 Pc  = 0.017); B*37:01 (OR = 8, Pc  = 1.811 × 10 −6 ); G*01:01 (OR = 3.61, Pc  = 2.839 × 10 −15 ) and G*01:06 (OR = 2.22, Pc  = 0.025); DQA1*01:05 (OR = 4.87, Pc  = 5.822 × 10 −5 ), DQA1*05:05 (OR = 2.64, Pc  = 9.114 × 10 −4 ), and DQA1*05:08 (OR = 10.2, Pc  = 0.016); DQB1*03:01 (OR = 1.69, Pc  = 0.048) and DQB1*05:01 (OR = 3.42, Pc  = 7.28 × 10 −6 ); and DRB1*10:01 (OR = 6.85, Pc  = 2.63 × 10 −6 ). To the contrary, HLA-DQA1*01:02 (OR = 0.46, Pc  = 8.603 × 10 −4 ) and DQA1*01:03 (OR = 0.38, Pc  = 0.048); DQB1*02:02 (OR = 0.28, Pc  = 0.016); and DRB1*07:01 (OR = 0.26, Pc  = 0.004) had significant associations with protection against BP. In addition, the frequency of haplotype HLA-DRB1*13-DQA1*05-DQB1*03 (OR = 12.32, Pc  = 0.026) in BP patients was significantly higher than those in controls. Conclusion Our data demonstrated that the alleles and haplotypes found in this study may be important differential genetic markers for susceptibility to or protection against BP in individuals of northern Chinese Han population. [ABSTRACT FROM AUTHOR]

Background Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. Objective This study aims to identify additional susceptibility variants associated with vitiligo at 11q23.3 in the Chinese Han population. Methods We selected and genotyped 26 SNPs at 11q23.3 in an independent cohort including 2924 cases and 4048 controls using the Sequenom MassArray iPLEX ® system. Bonferroni adjustment was used for multiple comparisons and P value <1.92 × 10 −3 (0.05/26) was considered statistically significant. Results The A allele of rs613791 and G allele of rs523604 located in CXCR5 were observed to be significantly associated with vitiligo (OR = 1.21, 95% CI: 1.11–1.31, P = 1.20 × 10 −5 ; OR = 1.14, 95% CI: 1.07–1.23, P = 1.90 × 10 −4 , respectively). The C allele of rs638893 (a previously reported one) located upstream of DDX6 was also significantly associated with vitiligo (OR = 1.25, 95% CI: 1.12–1.38, P = 3.04 × 10 −5 ). The genotypes distribution of 3 SNPs also showed significant differences between case and control (rs613791: P = 7.00 × 10 −6 , rs523604: P = 4.00 × 10 −3 , rs638893: P = 1.20 × 10 −5 , respectively). The two newly identified SNPs (rs613791 and rs523604) showed independent associations with vitiligo by linkage disequilibrium analysis and conditional logistic regression. Conclusions The study identified two new independent signals in the associated locus 11q23.3 for vitiligo. The presence of multiple independent variants emphasizes an important role of this region in disease susceptibility. [ABSTRACT FROM AUTHOR]