The PTPN22 620W allele confers susceptibility to systemic sclerosis: Findings of a large case–control study of European Caucasians and a meta‐analysis

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Abstract
Objective To determine whether genetic variants of the PTPN22 gene, including the R620W (1858C>T) missense single‐nucleotide polymorphism (SNP), are associated with systemic sclerosis (SSc). Since PTPN22 is involved in multiple autoimmune diseases, we also examined the occurrence of a concomitant autoimmune disease. We then conducted a meta‐analysis of the most recent studies of SSc in order to verify the association or lack of association between the PTPN22 1858C>T variant and SSc. Methods Seven PTPN22 SNPs were analyzed in a French Caucasian cohort of 659 SSc patients and 504 healthy controls. All SSc patient sera were tested for the presence of autoantibodies against topoisomerase I (anti–topo I) and for anticentromere antibodies (ACAs). Results The co‐occurrence of an autoimmune disease was observed in 22% of the 416 SSc patients who were exhaustively screened. In 33 of the 416 patients (8%), the concomitant autoimmune disease was known to be associated with PTPN22 1858T; these patients were excluded prior to analysis. No association was detected for any of the SNPs tested. PTPN22 haplotype analysis identified a strong association between SSc and the presence of a risk haplotype carrying the 1858T allele (P = 1.52 × 10–7) and a protective haplotype carrying the 1858C allele (P = 2.20 × 10–16) in our French Caucasian population. The meta‐analysis provided evidence that the PTPN22 1858T allele is involved in the genetic susceptibility to SSc in Caucasian (P = 8.39 × 10–3, OR 1.08 [95% CI 1.02–1.15]) and mixed (P = 3.11 × 10–3, OR 1.09 [95% CI 1.04–1.16]) populations, particularly in the anti–topo I–positive subset. Conclusion Our results indicate that PTPN22, a shared genetic factor of multiple autoimmune diseases, also contributes to the genetic background of SSc.