PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort. - Université de Bretagne Occidentale Accéder directement au contenu
Article Dans Une Revue Rheumatology Année : 2011

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

Résumé

OBJECTIVES: To investigate genotype-phenotype correlation and gene-environment 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-environment 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 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-environment 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.

Dates et versions

hal-00931447 , version 1 (15-01-2014)

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Carine Salliot, Karen Dawidowicz, Cédric Lukas, Mickael Guedj, Caroline Paccard, et al.. PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort.. Rheumatology, 2011, 50 (10), pp.1802-8. ⟨10.1093/rheumatology/ker224⟩. ⟨hal-00931447⟩
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