在一个中国汉族人群中，蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因多态性而非R620W与系统性红斑狼疮和类风湿关节炎的遗传易感性相关。
PTPN22 polymorphisms, but not R620W, were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population.
作者信息
Tang Liang, Wang Yan, Zheng Shui, Bao Meihua, Zhang Qingsong, Li Jianming
机构信息
Department of Human Anatomy, Histology and Embryology, Institute of Neuroscience, Changsha Medical University, Changsha, PR China; School of Basic Medical Science, Changsha Medical University, Changsha, PR China.
Key Laboratory for Fertility Regulation and Birth Health of Minority Nationalities of Yunnan Province, Judicial Expertise Center, Yunnan Population and Family Planning Research Institute, Kunming, PR China.
出版信息
Hum Immunol. 2016 Aug;77(8):692-698. doi: 10.1016/j.humimm.2016.04.021. Epub 2016 May 7.
OBJECTIVES
The present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.
METHODS
7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.
RESULTS
Rs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: padj = 6.07e-004, OR=0.57; rs3811021C: padj = 4.68e-005, OR=0.65) and RA (rs1217414T: padj = 2.01e-008, OR=0.26; rs3811021C: padj = 0.028, OR=0.70). And the rs3765598 revealed a strong risk factor for SLE (p=9.38e-009, padj = 6.57e-008, OR=1.93), but not for RA (p=0.48, OR=1.12). Moreover, protective haplotype ACTTC in RA (p=7.73e-016, padj = 5.51-015, OR[95%CI]=0.02[0.002-0.10]) and SLE (p=8.29e-018, padj = 5.80e-017, OR[95%CI]=0.11[0.06-0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p=0.0006, padj = 0.004, OR[95%CI]=1.85[1.29-2.63]; GCTTT: p=2.62e-005, padj = 1.85e-004, OR[95%CI]=2.40[1.57-3.65]) and SLE (ACGTC: p=0.0006, padj = 0.004, OR[95%CI]=1.85[1.29-2.63]; ACGTC: p=7.74e-011, padj = 6.81e-010, OR[95%CI]=2.21[1.12-3.34]; GCTTT: p=2.40[1.57-3.65], padj = 2.26e-006, OR[95%CI]=2.64[1.79-3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.
CONCLUSIONS
Our data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.
目的
本研究旨在检测中国汉族人群中蛋白酪氨酸磷酸酶非受体型22（PTPN22）基因多态性与类风湿关节炎（RA）及系统性红斑狼疮（SLE）之间可能存在的关联。
方法
采用限制性片段长度多态性（RFLP）方法，对358例RA患者、713例SLE患者以及564例RA对照和672例SLE对照进行7个PTPN22单核苷酸多态性（SNP）的基因分型。对整个数据集进行关联分析。同时也研究了RA和SLE患者临床特征与SNP之间的显著关系。
结果
在本研究中，rs2476601在SLE和RA患者以及健康对照中均缺乏多态性，频率均≤0.1%。PTPN22基因的两个SNP，即rs1217414和rs3811021，与SLE（rs1217414T：校正P值=6.07×10⁻⁴，比值比[OR]=0.57；rs3811021C：校正P值=4.68×10⁻⁵，OR=0.65）和RA（rs1217414T：校正P值=2.01×10⁻⁸，OR=0.26；rs3811021C：校正P值=0.028，OR=0.70）均显示出强关联。rs3765598显示是SLE的一个强风险因素（P=9.38×10⁻⁹，校正P值=6.57×10⁻⁸，OR=1.93），但对RA不是（P=0.48，OR=1.12）。此外，在RA（P=7.73×10⁻¹⁶，校正P值=5.51×10⁻¹⁵，OR[95%可信区间]=0.02[0.002 - 0.10]）和SLE（P=8.29×10⁻¹⁸，校正P值=5.80×10⁻¹⁷，OR[95%可信区间]=0.11[0.06 - 0.21]）中均观察到保护性单倍型ACTTC。另外，RA（ACGTC：P=0.0006，校正P值=0.004，OR[95%可信区间]=1.85[1.29 - 2.63]；GCTTT：P=2.62×10⁻⁵，校正P值=1.85×10⁻⁴，OR[95%可信区间]=2.40[1.57 - 3.65]）和SLE（ACGTC：P=0.0006，校正P值=0.004，OR[95%可信区间]=1.85[1.29 - 2.63]；ACGTC：P=7.74×10⁻¹¹，校正P值=6.81×10⁻¹⁰，OR[95%可信区间]=2.21[1.12 - 3.34]；GCTTT：P=2.40[1.57 - 3.65]，校正P值=2.26×10⁻⁶，OR[95%可信区间]=2.64[1.79 - 3.87]）中风险单倍型ACGTC和GCTTT的分布与对照有显著差异。此外，在SLE中观察到PTPN22 rs3765598与抗核抗体1（ANA1）之间存在显著关联。
结论
我们的数据提供了强有力的证据，表明PTPN22基因中的rs1217414和rs3811021可能是中国汉族人群中SLE和RA易感性的常见保护因素。而rs3765598可能增加SLE的遗传易感性，但不增加RA的遗传易感性。
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