NLRP3 AND CARD8 POLYMORPHISMS INFLUENCE HIGHER DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS

作者：Jenko Barbara; Praprotnik Sonja; Tomsic Matija; Dolzan Vita^*

来源：Journal of Medical Biochemistry, 2016, 35(3): 319-323.

DOI：10.1515/jomb-2016-0008

• polymorphism
• rheumatoid arthritis
• inflammasome
• BIRC5
• NLRP3

Background: The activation of NLRP3-inflammasome may contribute to inflammatory processes in rheumatoid arthritis (RA). Functional polymorphisms in the genes coding for its components NLRP3 and CARD8 were associated with a proinflammatory phenotype. Our aim was to investigate the influence of these polymorphisms on RA susceptibility and disease activity at the time of diagnosis and after six months of treatment.
Methods: A group of 128 RA patients treated with methotrexate and 122 healthy controls were genotyped for NLRP3 rs35829419 (p. Q705K) and CARD8 rs2043211 (p. C10X) polymorphisms.
Results: RA susceptibility was not influenced by the investigated polymorphisms or their interaction. The investigated polymorphisms explained 8% of variability in DAS28 at the time of diagnosis. Carriers of NLRP3 rs35829419 or CARD8 rs2043211 polymorphisms had significantly higher DAS28 at the time of diagnosis (p=0.003; p=0.022; respectively). Polymorphic CARD8 rs2043211 TT genotype was also associated with higher DAS28 after six months of treatment (p=0.033).
Conclusions: Genetic variability of inflammasome components may contribute to higher disease activity at the time of diagnosis and after 6 months of methotrexate treatment in RA patients. Better understanding of the immunological mechanisms behind a more active course of RA may suggest novel treatment approaches in a subset of patients with a proinflammatory phenotype.

• 出版日期2016-9