Background The protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene encodes a lymphoid-specific phosphatase (Lyp). Lyp is an intracellular PTP, and physically binds through its proline-rich motif to the SH3 domain of Csk kinase, which is an important suppressor of kinases that mediate T cell activation. The PTPN22 1858C->T SNP changes the amino acid at position 620 from an arginine (R) to a tryptophan (W) and disrupts the interaction between Lyp and Csk, and thus, inhibits complex formation and suppresses T cell activation.
Objectives The aim of this study was to determine whether the PTPN22 C1858T polymorphism confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities.
Methods MEDLINE database and manual search were utilized to identify to identify articles in which the PTPN22 polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the PTPN22 C1858T polymorphism and RA using; 1) allelic contrast, 2) dominant model.
Results A total of 30 separate comparisons involving 17,961 RA patients and 18,611 controls were considered in this meta-analysis. Meta-analysis showed an association between the T allele and RA in all subjects (OR = 1.490, 95% CI = 1.332 – 1.668, P < 1.0x10-9). After stratification by ethnicity, analysis indicated that the T allele was significantly associated with RA in Europeans and in Non-Europeans (OR = 1.423, 95% CI = 1.260 – 1.605, P = 1.0x10-8; OR = 1.902, 95% CI = 1.488 – 2.430, P = 2.8x10-8). Meta-analysis of the CT + TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and -negative subjects revealed a significant association with the T allele in RA patients with RF, but not in subjects without RF (OR = 1.561, 95% CI = 1.373 – 1.775, P < 1.0x10-9).
Conclusions This meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans, and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients
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Gregersen PK. Pathways to gene identification in rheumatoid arthritis: PTPN22 and beyond. Immunological reviews 2005;204:74-86.
Disclosure of Interest None Declared