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AB0218 IL-6, IL-1A and TNF-α Gene Polimorphism in Children with Juvenile Idiopathic Arthritis
  1. A. Lazareva1,2,
  2. J. Eglite1,
  3. S. Zadoroznijs3,4,
  4. Z. Davidsone1,
  5. R. Santere2,
  6. D. Berzina2,
  7. V. Staneivca1
  1. 1Riga Stradins University
  2. 2Children's University hospital
  3. 3University of Latvia
  4. 4Hospital of Traumatology and Orthopaedics, Riga, Latvia

Abstract

Background Juvenile idiopathic arthritis (JIA) is group of heterogenous diseases [1]. Inflammatory cytokines, like Iiterleukin 6 (IL-6), IL-1 and tumor necrosis factor alpha (TNF-a) and their regulatory gene polymorphisms can affect cytokine production, inflammatory processes and disease outcome [2-4].

Objectives To determine the association of IL6, IL1A and TNFA gene SNPs with JIA.

Methods All 107 JIA patients (28 seronegative and 12 seropositive polyarthritis, 23 persistent and 14 extended oligoarthritis, 24 enthesitis related arthritis and 6 systemic JIA) and 112 healthy controls were determined for IL6 gene promoter polymorphisms in -174GG, -174GC and -174CC positions, IL1A gene promoter SNP in -889CC, -889CT and -889TT positions, as well as the TNFA gene polymorphisms -308A/G, -238A/G and +489A using real-time polymerase chain reaction (RT-PCR) (QuantiFast Probe RT-PCR Kit Plus Applied Biosystems). Each potential SNP genotype distribution and association was compared between the different types of JIA and control group using Mann - Whitney test, chi-square test, Fisher's exact test.

Results We found significant differences in IL-6 -174GC and -174GG genotype distribution between JIA patients and controls (OR=0,8; p=0,0001 and OR=11.6; p=0.0001 respectively). Among JIA subtypes IL-6 SNP -174GC was less common in seronegative and seropositive polyarthritis, oligoarthritis, enthesitis related arthritis and systemic JIA patients (p<0,005), but genotype -174GG was more common in seronegative and seropositive polyarthritis, oligoarthritis and enthesitis related arthritis patients (p<0,005). TNFA gene SNPs -308AG and +489A were less common found in JIA patient group compared to controls (OR=0.02; p=0.0001 and OR=0.16; p=0.0001, respectively). Among JIA subtypes weak association with +489A genotype and persistent oligoarthritis and enthesitis related arthritis patients was found (p=0,0703 and p=0,0610 respectively). IL1A gene polymorphisms had no significant difference between JIA controls and JIA subtypes but genotype -899CC had weak association with seronegative polyarthritis (OR=2,18; p=0,0796).

Conclusions

  • IL6 gene polymorphism IL-6 -174GC and TNFA gene SNPs -308AG and +489A were less common found in JIA patient group.

  • IL6 gene polymorphism -174GG was more common found in JIA patient group and it may contribute to susceptibility to JIA.

  • To obtain more accurate data on the regulatory cytokine gene polymorphisms in the pathogenesis of JIA, additional studies with larger cohorts are needed.

References

  1. Petty R.E., Southwood T.R., Manners P. Et al.: Intrenational League of Associations of Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390-2.

  2. Cytokine and Growth Factor Reviews. 2009;20

  3. De Benedetti F, Rucci N, Del Fattore A, et al. Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis Rheum 2006;54:3551-3563.

  4. Dinarello CA. The many worlds of reducing interleukin-1 [editorial] 2005;52:1960–7.

Disclosure of Interest None declared

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