Association Study and Fine-Mapping Major Histocompatibility Complex Analysis of Pemphigus Vulgaris in a Han Chinese Population
Autor: | Sen Yang, Yujun Sheng, Xianfa Tang, Caihong Zhu, Xiaoqun Luo, Wenjun Wang, Yang Li, Fusheng Zhou, Yaohua Zhang, Xuejun Zhang, Xiaodong Zheng, Xianbo Zuo, Shengxiu Liu, Dong-Qing Ye, Sheng-an Chen, Gang Chen, Qian Wenjun, Fanping Yang, Zhengwei Zhu, Hui Cheng, Huayang Tang, Jinping Gao, Liangdan Sun, Zaixing Wang, Qinyuan Zhu |
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Rok vydání: | 2018 |
Předmět: |
Male
Risk 0301 basic medicine China Genotype Autoimmunity HLA-DR alpha-Chains Genome-wide association study Locus (genetics) Single-nucleotide polymorphism Dermatology Biology Polymorphism Single Nucleotide Biochemistry Major Histocompatibility Complex 03 medical and health sciences Gene Frequency ATP Binding Cassette Transporter Subfamily B Member 3 Genetic predisposition Humans Genetic Predisposition to Disease Molecular Biology Allele frequency Genetic Association Studies Genetics Principal Component Analysis Cell Biology Odds ratio 030104 developmental biology Expression quantitative trait loci biology.protein TAP2 Female Pemphigus Genome-Wide Association Study HLA-DRB1 Chains |
Zdroj: | Journal of Investigative Dermatology. 138:2307-2314 |
ISSN: | 0022-202X |
Popis: | 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. |
Databáze: | OpenAIRE |
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