Jerzy Swierkot1, Katarzyna Bogunia-Kubik2, Beata Nowak3, Katarzyna Bialowas4, Lucyna Korman4, Katarzyna Gebura2, Katarzyna Kolossa5, Slawomir Jeka5, Piotr Wiland4. 1. Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland. Electronic address: jurekswierkot0@poczta.onet.pl. 2. Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. 3. Department of Pharmacology, Wroclaw Medical University, Wroclaw, Poland; Department of Rheumatology and Internal Medicine, Wroclaw University Hospital, Wroclaw, Poland. 4. Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland. 5. Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela Bydgoszcz, Wroclaw, Poland.
Abstract
INTRODUCTION: Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. METHODS: Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. RESULTS: At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. CONCLUSIONS: Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
INTRODUCTION: Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. METHODS: Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1BT676G) were determined in 280 RApatients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. RESULTS: At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. CONCLUSIONS: Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
Authors: Dmitry S Mikhaylenko; Marina V Nemtsova; Irina V Bure; Ekaterina B Kuznetsova; Ekaterina A Alekseeva; Vadim V Tarasov; Alexander N Lukashev; Marina I Beloukhova; Andrei A Deviatkin; Andrey A Zamyatnin Journal: Int J Mol Sci Date: 2020-07-11 Impact factor: 5.923
Authors: Katarzyna Gębura; Jerzy Świerkot; Barbara Wysoczańska; Lucyna Korman; Beata Nowak; Piotr Wiland; Katarzyna Bogunia-Kubik Journal: Int J Mol Sci Date: 2017-07-04 Impact factor: 5.923