Rodríguez-Rodríguez Luis, Taib Wan Rohani Wan, Topless Ruth, Steer Sophia, González-Escribano María F, Balsa Alejandro, Pascual-Salcedo Dora, González-Gay Miguel A, Raya Enrique, Fernandez-Gutierrez Benjamín, González-Álvaro Isidoro, Bottini Nunzio, Witte Torsten, Viken Marte K, Coenen Marieke J H, van Riel Piet L C M, Franke Barbara, den Heijer Martin, Radstake Timothy R D J, Wordsworth Paul, Lie Benedicte A, Merriman Tony R, Martín Javier
Instituto de Parasitología y Biomedicina Lopez-Neyra, CSIC, Armilla and Hospital Clínico San Carlos, Madrid, Spain.
Arthritis Rheum. 2011 Feb;63(2):365-72. doi: 10.1002/art.30145.
Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA).
RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5'-allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined.
The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel-Haenszel pooled OR 0.80 [95% CI 0.67-0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05-1.55], for 3 versus 1 risk allele P = 6.67 × 10(-11) , OR 2.01 [1.63-2.48], and for 4 versus 1 risk allele P = 6.50 × 10(-11) , OR 3.55 [2.42-5.20]).
Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well-established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.
最近发现一种功能性蛋白酪氨酸磷酸酶非受体型22（PTPN22）变体（R263Q；rs33996649）与系统性红斑狼疮（SLE）相关。本研究旨在分析这种多态性对类风湿关节炎（RA）风险的影响。
从6个不同国家（西班牙、新西兰、英国、挪威、荷兰和德国）的门诊招募了RA患者（n = 5579）。从相同地区招募了健康对照者（n = 5392）。有100%的把握度检测到与SLE中观察到的效应相当的效应。使用TaqMan 5'等位基因鉴别分析对样本进行PTPN22 R263Q（rs33996649）和PTPN22 R620W（rs2476601）多态性的基因分型。使用Unphased和Stata 10软件单独分析R263Q变体的效应，并结合R620W的效应进行分析。确定比值比（OR）和95%置信区间（95%CI）。
在对6个群体的汇总分析中，PTPN22 R263Q的次要等位基因A与较低的RA风险显著相关（P = 0.016，Mantel-Haenszel汇总OR 0.80 [95%CI 0.67 - 0.96]），独立于R620W多态性的效应。两种多态性具有累加效应。携带的RA风险等位基因越多（R263Q G等位基因，R620W T等位基因），RA风险越高（2个风险等位基因与1个风险等位基因相比，P = 0.014，OR 1.28 [95%CI 1.05 - 1.55]；3个风险等位基因与1个风险等位基因相比，P = 6.67×10⁻¹¹，OR 2.01 [1.63 - 2.48]；4个风险等位基因与1个风险等位基因相比，P = 6.50×10⁻¹¹，OR 3.55 [2.42 - 5.20]）。
我们的研究结果表明，PTPN22 R263Q多态性的次要等位基因与较低的RA风险相关。这种关联独立于PTPN22 R620W与RA之间已确立的关联。两种多态性对RA风险具有累加效应。
