Gourh Pravitt, Tan Filemon K, Assassi Shervin, Ahn Chul W, McNearney Terry A, Fischbach Michael, Arnett Frank C, Mayes Maureen D
University of Texas Health Science Center at Houston, TX 77030, USA.
Arthritis Rheum. 2006 Dec;54(12):3945-53. doi: 10.1002/art.22196.
To determine any associations of the PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals.
A total of 850 white, 130 black, 120 Hispanic, and 20 Choctaw Indian patients with SSc were compared with 430 white, 164 black, 146 Hispanic, and 76 Choctaw Indian control subjects, respectively. All subjects were living in the US. PTPN22 SNP (rs2476601) genotyping was performed by TaqMan 5' allelic discrimination assay and pyrosequencing.
The PTPN22 CT/TT genotype showed significant association with anti-topo I antibody-positive SSc in white patients (odds ratio [OR] 2.21, 95% confidence interval [95% CI] 1.3-3.7) and with ACA-positive white patients with SSc (OR 1.70, 95% CI 1.1-2.7). Frequency of the PTPN22*T allele also showed significant association with anti-topo I antibody-positive SSc in white patients (OR 2.03, 95% CI 1.3-3.2). When data for patients in the 3 ethnic groups (black, white, and Hispanic) were combined, a significant association with both genotype and allele frequencies was observed, suggesting a trend toward association in ACA-positive and anti-topo I antibody-positive SSc. Stepwise logistic regression analysis (controlled for the confounding effects of sex and race) showed that the PTPN22 CT/TT genotype was associated with a significantly higher risk of SSc compared with the CC genotype (for patients with SSc, OR 1.64, 95% CI 1.2-2.2; for ACA-positive patients with SSc, OR 1.63, 95% CI 1.0-2.6; for anti-topo I antibody-positive SSc, OR 2.33, 95% CI 1.5-3.7).
Our results indicate that the PTPN22 R620W polymorphism is associated with ACA-positive and anti-topo I antibody-positive subsets of SSc and represents a risk factor in both white patients and black patients. The association of subsets of SSc with the PTPN22 R620W polymorphism further strengthens the classification of SSc within the spectrum of autoimmune diseases and strongly suggests the involvement of common susceptibility genes and similarly disordered immunoregulatory pathways.
在一项针对美国白人、黑人、西班牙裔和乔克托族印第安人的病例对照研究中，确定蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因R620W单核苷酸多态性（SNP）与系统性硬化症（SSc）或抗着丝点抗体（ACA）阳性或抗拓扑异构酶I（抗拓扑酶I）抗体阳性的SSc之间的任何关联。
分别将850例白人、130例黑人、120例西班牙裔和20例乔克托族印第安人SSc患者与430例白人、164例黑人、146例西班牙裔和76例乔克托族印第安人对照者进行比较。所有受试者均居住在美国。通过TaqMan 5'等位基因鉴别分析和焦磷酸测序法进行PTPN22 SNP（rs2476601）基因分型。
PTPN22 CT/TT基因型在白人患者中与抗拓扑酶I抗体阳性的SSc显著相关（比值比[OR] 2.21，95%置信区间[95%CI] 1.3 - 3.7），与ACA阳性的白人SSc患者相关（OR 1.70，95%CI 1.1 - 2.7）。PTPN22*T等位基因频率在白人患者中也与抗拓扑酶I抗体阳性的SSc显著相关（OR 2.03，95%CI 1.3 - 3.2）。当合并3个种族（黑人、白人和西班牙裔）患者的数据时，观察到基因型和等位基因频率均有显著关联，提示在ACA阳性和抗拓扑酶I抗体阳性的SSc中有关联趋势。逐步逻辑回归分析（控制性别和种族的混杂效应）显示，与CC基因型相比，PTPN22 CT/TT基因型与SSc风险显著更高相关（对于SSc患者，OR 1.64，95%CI 1.2 - 2.2；对于ACA阳性的SSc患者，OR 1.63，95%CI 1.0 - 2.6；对于抗拓扑酶I抗体阳性的SSc患者，OR 2.33，95%CI 1.5 - 3.7）。
我们的结果表明，PTPN22 R620W多态性与ACA阳性和抗拓扑酶I抗体阳性的SSc亚组相关，是白人和黑人患者的一个风险因素。SSc亚组与PTPN22 R620W多态性的关联进一步强化了SSc在自身免疫性疾病谱中的分类，并强烈提示存在共同的易感基因和类似紊乱的免疫调节途径。
