Bowes John, Loehr Sabine, Budu-Aggrey Ashley, Uebe Steffen, Bruce Ian N, Feletar Marie, Marzo-Ortega Helena, Helliwell Philip, Ryan Anthony W, Kane David, Korendowych Eleanor, Alenius Gerd-Marie, Giardina Emiliano, Packham Jonathan, McManus Ross, FitzGerald Oliver, Brown Matthew A, Behrens Frank, Burkhardt Harald, McHugh Neil, Huffmeier Ulrike, Ho Pauline, Reis Andre, Barton Anne
Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Institute of Human Genetics, University of Erlangen-Nuremberg, Erlangen, Germany.
Ann Rheum Dis. 2015 Oct;74(10):1882-5. doi: 10.1136/annrheumdis-2014-207187. Epub 2015 Apr 28.
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA.
A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10(-4)) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity.
We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10(-9), OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10(-4)). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10(-9)).
For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis.
银屑病关节炎（PsA）是一种与银屑病相关的慢性炎症性关节炎；据估计，其遗传成分比单纯的银屑病更高，然而，迄今为止确定的大多数PsA遗传易感性位点也与银屑病共有。在此，我们试图验证从我们最近的PsA免疫芯片研究中选出的新型单核苷酸多态性，并确定其对PsA的特异性。
共选择了15个单核苷酸多态性（免疫芯片<1×10⁻⁴），使用TaqMan技术在1177例患者和2155例对照中进行验证基因分型。免疫芯片和验证数据集的荟萃分析包括3139例PsA患者和11078例对照。将新的PsA易感位点与两项大型银屑病研究（WTCCC2和免疫芯片）的数据进行比较，以确定PsA的特异性。
我们发现与rs2476601存在全基因组显著关联，该位点定位于PTPN22（p = 1.49×10⁻⁹，OR = 1.32），但在银屑病队列中没有关联证据（p = 0.34），并且PsA和银屑病之间的效应估计值存在显著差异（p = 3.2×10⁻⁴）。此外，我们发现与先前报道的银屑病风险位点NOS2（rs4795067，p = 5.27×10⁻⁹）存在全基因组显著关联。
我们首次报道PTPN22（rs2476601）与PsA易感性存在全基因组显著关联，但没有证据表明其与银屑病有关联。
