Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients.
Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients.
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DOI：
10.1186/ar1945
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发表时间：
2006
影响因子：
4.9
通讯作者：
Wagner, Ulf
中科院分区：
文献类型：
--
作者：
Pierer, Matthias;Kaltenhauser, Sylke;Arnold, Sybille;Wahle, Matthias;Baerwald, Christoph;Hantzschel, Holm;Wagner, Ulf
PTPN 22基因的功能性单核苷酸多态性（SNP）是类风湿关节炎（RA）的易感基因。本文介绍的研究描述了PTPN 22 1858 T等位基因与德国患者队列中RA的相关性; 390例RA患者和349例对照患者入组研究。对于123例患者，从疾病发作起6年以上的临床和影像学记录可用。使用基于限制性片段长度多态性PCR的基因分型试验对PTPN 22 1858 SNP进行基因分型。PTPN 22 1858 T等位基因携带者发生RA的优势比为2.57（95%置信区间（CI）1.85-3.58，p < 0.001），纯合子为5.58（95% CI 1.85-16.79）。PTPN 22 1858 T等位基因不仅与类风湿因子（RF）和抗环瓜氨酸肽（CCP）阳性的RA相关，而且与RF和抗CCP阴性的疾病相关。PTPN 22 1858 T等位基因的频率在男性患者中不成比例地增加（53.8%，而女性患者中为33.0%，p < 0.001），并且由此产生的男性携带者的优势比增加至4.47（95%CI 2.5-8.0，p < 0.001）。此外，在男性患者群体中，罕见等位基因与HLA-DRB 1共享表位显著相关（p = 0.01）。在疾病活动或Larsen评分中没有检测到显著差异。结果提供了进一步的证据，PTPN 22 1858 T等位基因与RA相关，而与自身抗体的产生无关。男性患者中风险等位基因的频率增加及其与共享表位的相关性表明，男性对疾病发病机制的遗传贡献可能更为突出。
The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123 patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85–3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85–16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5–8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might be more prominent in men.