PTPN22 Polymorphisms, but Not R620W, Were Associated with the Genetic Susceptibility of Systemic Lupus Erythematosus and Rheumatoid Arthritis in a Chinese Han Population

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.