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Association Study and Fine-Mapping Major Histocompatibility Complex Analysis of Pemphigus Vulgaris in a Han Chinese Population. 2018
Jinping Gao, and
Caihong Zhu, and
Yaohua Zhang, and
Yujun Sheng, and
Fanping Yang, and
Wenjun Wang, and
Wenjun Qian, and
Sheng'an Chen, and
Qinyuan Zhu, and
Xianbo Zuo, and
Huayang Tang, and
Xianfa Tang, and
Yang Li, and
Hui Cheng, and
Fusheng Zhou, and
Shengxiu Liu, and
Gang Chen, and
Xiaodong Zheng, and
Zhengwei Zhu, and
Zaixing Wang, and
Sen Yang, and
Xiaoqun Luo, and
Dongqing Ye, and
Xuejun Zhang, and
Liangdan Sun
Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui Province, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui Province, China; State Key Lab of Dermatology Incubation Center, Anhui Medical University, Hefei, Anhui Province, China.
To identify possible additional genetic susceptibility loci for pemphigus vulgaris (PV), we performed a genome-wide association study of 240 PV patients and 1,031 control individuals, and we selected the top single nucleotide polymorphisms for replication in independent samples, with 252 patient samples and 1,852 control samples. We identified rs11218708 (P = 3.1 × 10-8, odds ratio = 1.54) at chromosome locus 11q24.1 as significantly associated with PV. A fine-mapping analysis of PV risk in the major histocompatibility complex region showed three independent variants predisposed to PV using stepwise analysis: HLA-DRB1*14:04 (P = 2.47 × 10-38, odds ratio = 6.28), rs7454108 at the TAP2 gene (P = 2.78 × 10-12, odds ratio = 3.25), and rs1051336 at the HLA-DRA gene (P = 3.06 × 10-6, odds ratio = 0.33). A systematic evaluation using gene- and pathway-based analyses showed a high tendency for PV susceptibility genes to be associated with autoimmunity. Our study highlights the involvement of immune-mediated processes in the pathophysiology of PV and illustrates the value of imputation to identify variants in the major histocompatibility complex region.
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