PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort

Abstract

These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA.

A Constitutional Activating MET Mutation Makes the Genetic Link between Malignancies and Chronic Inflammatory Diseases

“…As a whole, these clinical and experimental results open the way for a new targeted therapy consisting in testing MET inhibitors, already available in clinical practice, among patients with rheumatoid arthritis, Sj€ ogren syndrome, and MET pathway activation. A preliminary step is to assess the incidence of constitutional pR988C, c2962C>T MET mutation in cohorts of patients with rheumatoid arthritis or Sj€ ogren syndrome, using cohorts like the French "ESPOIR" cohort, which includes patients with early arthritis followed up over a number of years (23,24).…”

Metaanalysis of the Association of Smoking andPTPN22R620W Genotype on Autoantibody Status and Radiological Erosions in Rheumatoid Arthritis

“…Subjects meeting the American College of Rheumatology 1987 criteria for RA 13 with available genotyping data on rs2476601, smoking, and ACPA or erosions were compiled from the following RA populations: Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) 14 , Early RA study (ERAS) 15 , Evaluation et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) 11 , Norfolk Arthritis Register (NOAR) 16 , UK RA Genetics (UKRAG; London, Manchester, and Sheffield) 17 , and Yorkshire Early RA (YEAR) 18 . Subjects meeting the American College of Rheumatology 1987 criteria for RA 13 with available genotyping data on rs2476601, smoking, and ACPA or erosions were compiled from the following RA populations: Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) 14 , Early RA study (ERAS) 15 , Evaluation et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) 11 , Norfolk Arthritis Register (NOAR) 16 , UK RA Genetics (UKRAG; London, Manchester, and Sheffield) 17 , and Yorkshire Early RA (YEAR) 18 .…”

“…The Journal of on June 7, 2015 -Published by www.jrheum.org Downloaded from larger protective effect when subjects ever smoked in combination with carrying at least 1 of the PTPN22 single amino acid changes R620W (rs2476601) 11 . This protective effect of smoking and the PTPN22 risk allele on radiological damage had not been previously reported.…”

“…Despite this, 2 recent studies 11,12 (n = 532 and n = 156, respectively) found no evidence that smoking increased the risk of being ACPA-positive. One of those studies also reported a protective effect of smoking on the development of bone erosions in subjects who had ever smoked and a…”

Early lessons from the recent-onset rheumatoid arthritis cohort ESPOIR

“…However, the potential effect of smoking on the course of the disease remains controversial. A study of the ESPOIR cohort suggests that both smoking and menopausal hormone therapy may protect against the development of anticitrullinated protein antibodies (ACPAs) and of early bone erosions, in the absence of patent interactions with the genetic background [5]. Along the same line, cigarette smoke exposure seemed to protect against radiographic progression during three years of follow-up [6].…”