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Zuo X.,Anhui Medical University | Zuo X.,Fudan University | Zuo X.,State Key Laboratory Incubation of Dermatology | Zuo X.,Key Laboratory of Dermatology | And 127 more authors.
Nature Communications | Year: 2015

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10-08). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis. © 2015 Macmillan Publishers Limited. All rights reserved.

Wang W.-J.,Anhui Medical University | Wang W.-J.,Key Laboratory of Dermatology | Wang W.-J.,State Key Laboratory Incubation of Dermatology | Yin X.-Y.,Anhui Medical University | And 20 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2013

Background Psoriasis is a common chronic inflammatory skin disease. IL23/Th17 is a newly confirmed pathway in psoriasis. Objective To investigate the gene-gene interactions in IL23/Th17 pathway underlying psoriasis. Methods A total of 299 single-nucleotide polymorphisms from 11 genes in IL23/Th17 pathway were genotyped on 1139 patients with psoriasis and 1694 controls. Multifactor dimensionality reduction and logistic regression algorithms were applied to explore the gene-gene interactions. Results We found that there were a three-way interaction among IL21, CCR4 and TNF(χ2 = 5.02(1), P = 0.025) and three pair-wise gene-gene interactions between IL12RB1 and CCR4(χ2 = 11.66(4), P = 0.0201), IL22 and CCR4 (χ2 = 11.97(4), P = 0.0176), IL12RB1 and IL6 (χ2 = 7.31(1), P = 0.0069) in psoriasis. Conclusions Our results might be helpful for explaining the missing heritability of the psoriasis due to epistasis and provide a deep insight into the important role of the IL23/Th17 pathway in the pathogenesis of psoriasis. © 2012 European Academy of Dermatology and Venereology.

Zhao Y.,Anhui Medical University | Zhao Y.,Key Laboratory of Dermatology | Zhang B.,Anhui Medical University | Lei Y.,Anhui Medical University | And 9 more authors.
Tumor Biology | Year: 2016

The spliceosome machinery composed of multimeric protein complexes guides precursor messenger RNAs (mRNAs) (pre-mRNAs) splicing in eukaryotic cells. Spliceosome components have been shown to be downregulated in cancer and could be a promising molecular target for anticancer therapy. The ubiquitin-specific protease 39 (USP39) is essential for pre-mRNA splicing, and upregulated USP39 expression is noted in a variety of cancers. However, the role of USP39 in the development and progression of melanoma remains unclear. In the present study, USP39 expression was found to be increased in melanoma tissues compared with that in nevus tissues. USP39 silencing via lentivirus-mediated short hairpin RNA (shRNA) significantly suppressed melanoma cell proliferation, induced G0/G1 cell cycle phase arrest, and increased apoptosis in vitro. Moreover, USP39 knockdown suppressed melanoma tumor growth in a xenograft model. In addition, USP39 silencing was associated with the increased expressions of p21, p27, and Bax. Furthermore, the inhibition of USP39 expression decreased the phosphorylation of extracellular signal-regulated kinase (ERK)1/2, indicating that ERK signaling pathways might be involved in the regulation of melanoma cell proliferation by USP39. Our findings suggest that USP39 may play crucial roles in the development and pathogenesis of melanoma, and it may serve as a potential therapeutic target for melanoma. © 2016 International Society of Oncology and BioMarkers (ISOBM)

Hu W.,Anhui Medical University | Hu W.,Key Laboratory of Dermatology | Sun L.,Anhui Medical University | Sun L.,Key Laboratory of Dermatology | And 31 more authors.
Rheumatology International | Year: 2011

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with complex genetic inheritance. IKZF1 was established as a new susceptibility gene for SLE in a recent genome-wide association study (GWAS) in Chinese Han population. In order to examine whether expression levels of IKZF1 contribute to the pathogenesis of SLE, we estimated IKZF1 mRNA expression levels in peripheral blood mononuclear cells (PBMCs) via fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) in 60 patients with SLE and 60 controls. We also explored whether the IKZF1 mRNA expression levels are associated with the variant of the SNP rs4917014 and the SLE Disease Activity Index (SLEDAI). The expression levels of IKZF1 mRNA in patients with SLE were significantly decreased compared with those in healthy controls (P < 0.001). No significant differences were found between IKZF1 mRNA expression levels and SLEDAI scores, SNP rs4917014. Our results suggest that decreased expression of IKZF1 mRNA may be correlated with the pathogenesis of SLE. © 2010 Springer-Verlag.

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