OBJECTIVE: Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed. METHODS: A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed. RESULTS: At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses. CONCLUSIONS: The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.
OBJECTIVE:Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed. METHODS: A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed. RESULTS: At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses. CONCLUSIONS: The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.
Authors: Chiea Chuen Khor; Sonia Davila; Willemijn B Breunis; Yi-Ching Lee; Chisato Shimizu; Victoria J Wright; Rae S M Yeung; Dennis E K Tan; Kar Seng Sim; Jie Jin Wang; Tien Yin Wong; Junxiong Pang; Paul Mitchell; Rolando Cimaz; Nagib Dahdah; Yiu-Fai Cheung; Guo-Ying Huang; Wanling Yang; In-Sook Park; Jong-Keuk Lee; Jer-Yuarn Wu; Michael Levin; Jane C Burns; David Burgner; Taco W Kuijpers; Martin L Hibberd Journal: Nat Genet Date: 2011-11-13 Impact factor: 38.330
Authors: R Prieto-Pérez; G Solano-López; T Cabaleiro; M Román; D Ochoa; M Talegón; O Baniandrés; J L López-Estebaranz; P de la Cueva; E Daudén; F Abad-Santos Journal: Pharmacogenomics J Date: 2016-09-27 Impact factor: 3.550
Authors: M Fabris; L Quartuccio; C Fabro; S Sacco; S Lombardi; R Ramonda; D Biasi; D Punzi; S Adami; I Olivieri; F Curcio; S De Vita Journal: Pharmacogenomics J Date: 2015-07-07 Impact factor: 3.550
Authors: Paula I Burgos; Maria I Danila; James M Kelley; Laura B Hughes; S Louis Bridges Journal: Ther Adv Musculoskelet Dis Date: 2009-04 Impact factor: 5.346
Authors: Aparna Chhibber; Deanna L Kroetz; Kelan G Tantisira; Michael McGeachie; Cheng Cheng; Robert Plenge; Eli Stahl; Wolfgang Sadee; Marylyn D Ritchie; Sarah A Pendergrass Journal: Pharmacogenomics Date: 2014-12 Impact factor: 2.533