Abstract:
Killer cell immunoglobulin-like receptors (KIR) regulate immune responses in NK and CD8+ T cells via 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)通过与HLA配体的相互作用调节NK和CD8+T细胞中的免疫应答。KIR基因,包括KIR2DS1,KIR3DL1和KIR3DS1以前曾被认为与银屑病易感性有关.然而,这些以前的研究仅限于小样本量,部分原因是KIR基因直接分型所需的时间和费用。这里,我们实施了KIR*IMP,从发现队列(n=11,912)的19号染色体上的单核苷酸多态性(SNPs),从PAGE联盟,加州大学旧金山分校,邓迪大学,以及来自北加利福尼亚KaiserPermanente的复制队列(n=66,357)。考虑患者血统和高风险HLA等位基因的分层多变量逻辑回归显示,在发现队列中,KIR2DL2拷贝数与银屑病显着相关(p≤0.05)。在KaiserPermanente复制队列中复制KIR2DL2拷贝数关联。这是首次报道的KIR2DL2拷贝数与银屑病的关联,并强调了KIR遗传学在银屑病发病机制中的重要性。