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

Abstract

Objectives: To investigate genotype-henotype correlation and gene-nvironment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients. Methods: An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-nvironment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI). Results: PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P<0.0001]. Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4 - .8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-nvironment interaction was detected. Conclusion: These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.