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在北美和欧洲银屑病病例对照队列中进行大规模的 KIR 拷贝数和 HLA 等位基因的推断揭示了抑制性 KIR2DL2 与银屑病的关联。

Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 With Psoriasis.

机构信息

Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.

Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, United States.

出版信息

Front Immunol. 2021 Jun 11;12:684326. doi: 10.3389/fimmu.2021.684326. eCollection 2021.

Abstract

Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells interaction with HLA ligands. KIR genes, including KIR2DS1, KIR3DL1, and KIR3DS1 have previously been implicated in psoriasis susceptibility. However, these previous studies were constrained to small sample sizes, in part due to the time and expense required for direct genotyping of KIR genes. Here, we implemented KIR*IMP to impute KIR copy number from single-nucleotide polymorphisms (SNPs) on chromosome 19 in the discovery cohort (n=11,912) from the PAGE consortium, University of California San Francisco, and the University of Dundee, and in a replication cohort (n=66,357) from Kaiser Permanente Northern California. Stratified multivariate logistic regression that accounted for patient ancestry and high-risk HLA alleles revealed that KIR2DL2 copy number was significantly associated with psoriasis in the discovery cohort (p ≤ 0.05). The KIR2DL2 copy number association was replicated in the Kaiser Permanente replication cohort. This is the first reported association of KIR2DL2 copy number with psoriasis and highlights the importance of KIR genetics in the pathogenesis of psoriasis.

摘要

杀伤细胞免疫球蛋白样受体(KIR)调节 NK 和 CD8+T 细胞与 HLA 配体的免疫反应。KIR 基因,包括 KIR2DS1、KIR3DL1 和 KIR3DS1,先前已被牵连到银屑病易感性中。然而,这些先前的研究受到样本量小的限制,部分原因是直接对 KIR 基因进行基因分型所需的时间和费用。在这里,我们在 PAGE 联盟、加利福尼亚大学旧金山分校和邓迪大学的发现队列(n=11912)和 Kaiser Permanente 北加利福尼亚的复制队列(n=66357)中,通过 19 号染色体上的单核苷酸多态性(SNP)实施了 KIR*IMP 来推断 KIR 拷贝数。经过分层多变量逻辑回归,考虑到患者的祖先和高风险 HLA 等位基因,发现 KIR2DL2 拷贝数与发现队列中的银屑病显著相关(p≤0.05)。KIR2DL2 拷贝数的关联在 Kaiser Permanente 复制队列中得到了复制。这是首次报道 KIR2DL2 拷贝数与银屑病的关联,突出了 KIR 遗传学在银屑病发病机制中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4a9/8231283/1018e3628112/fimmu-12-684326-g001.jpg

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