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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The PTPN22 620W allele confers susceptibility to systemic sclerosis: findings of a large case-control study of European Caucasians and a meta-analysis.

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 x 10(-7)) and a protective haplotype carrying the 1858C allele (P = 2.20 x 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 x 10(-3), OR 1.08 [95% CI 1.02-1.15]) and mixed (P = 3.11 x 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.[1]

References

  1. The PTPN22 620W allele confers susceptibility to systemic sclerosis: findings of a large case-control study of European Caucasians and a meta-analysis. Dieudé, P., Guedj, M., Wipff, J., Avouac, J., Hachulla, E., Diot, E., Granel, B., Sibilia, J., Cabane, J., Meyer, O., Mouthon, L., Kahan, A., Boileau, C., Allanore, Y. Arthritis Rheum. (2008) [Pubmed]
 
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