Systematic evaluation of association between the microsomal glutathione S-transferase 2 common variation and psoriasis vulgaris in Chinese population
ARCHIVES OF DERMATOLOGICAL RESEARCH
Authors: Yang, Sen; Yan, Kai-Lin; Zhang, Xue-Jun; Xiao, Feng-Li; Fan, Xing; Gao, Min; Cui, Yong; Wang, Peng-Guang; Zhang, Guo-Long; Sun, Liang-Dan; Wang, Zhi-Min; Wang, Da-Zhi; Zhang, Kai-Yue; Huang, Wei; Liu, Jian-Jun
Abstract
Several recent studies have demonstrated the possible involvement of the microsomal glutathione S-transferase 2 (MGST2) gene in the pathogenesis of psoriasis. The objectives of this work are to determine whether the genetic polymorphisms of the MGST2 gene were associated with an increased risk of psoriasis in Chinese patients. We first characterized the linkage disequilibrium pattern within MGST2 and identified single-nucleotide polymorphisms (SNPs) for tagging common genetic variants. Genotype- and haplotype-based analyses were then performed by genotyping the Tag SNPs in a large-scale sample of cases and controls. We characterized the linkage disequilibrium pattern within MGST2 using 12 densely distributed SNPs and identified 6 SNPs for tagging common genetic variants. We then performed an association analysis by genotyping the six SNPs in 552 cases and 384 controls, but none of the genotype- and haplotype-based analyses revealed significant evidence for association. We also performed family-based association analysis by genotyping the six SNPs in 95 trios; no evidence for association was identified. Our comprehensive genetic analysis of MGST2 common variants in a large Chinese sample of psoriasis did not provide any supporting evidence for MGST2 to be the susceptibility gene within the PSORS9 locus.
UVB drives different stages of epigenome alterations during progression of skin cancer
CANCER LETTERS
Authors: Yang, Yuqing; Wu, Renyi; Sargsyan, Davit; Yin, Ran; Kuo, Hsiao-Chen; Yang, Irene; Wang, Lujing; Cheng, David; Wang, Chao; Li, Shanyi; Hudlikar, Rasika; Lu, Yaoping; Kong, Ah-Ng
Abstract
Exposure to ultraviolet B (UVB) irradiation results in multitude of cellular responses including generation of reactive oxygen species and DNA damage and is responsible for non-melanoma skin cancers (NMSCs). Although genetic mutation is well documented, the epi-mutation, the alteration in epigenetics, remains elusive. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in UVB-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages. Methyl-seq and RNA-seq were performed to examine the methylation and corresponding transcriptome alterations. The methylation profiles in mouse epidermis were altered by UVB-irradiation as time progresses. Ingenuity Pathways Analysis (IPA) identified many cancer related pathways including PTEN, p53, Nrf2 and inflammatory signaling in UVB-irradiation induced carcinogenesis. Additionally, some novel genes involved in skin carcinogenesis that were not previously reported were differentially methylated, including Enf2, Mgst2, Vegfa, and Cdk4. Taken together, the current study provides novel profiles and insights of methylation and transcriptomic changes at different stages of carcinogenesis in UVB-irradiation induced NMSC and offers potential targets for prevention and treatment of NMSC at different stages of human skin cancer.