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Epistatic interaction between FCRL3 and NFκB1 genes in Spanish patients with rheumatoid arthritis
  1. A Martínez1,
  2. E Sánchez2,
  3. A Valdivia1,
  4. G Orozco2,
  5. M A López-Nevot3,
  6. D Pascual-Salcedo4,
  7. A Balsa5,
  8. B Fernández-Gutiérrez6,
  9. E G de la Concha1,
  10. A García-Sánchez7,
  11. B P C Koeleman8,
  12. E Urcelay1,
  13. J Martín2
  1. 1Immunology Department, Hospital Clinico San Carlos, Madrid, Spain
  2. 2Lopez-Neyra Biomedicine Institute, CSIC, Granada, Spain
  3. 3Immunology Department, Hospital Virgen de las Nieves, Granada
  4. 4Immunology Department, Hospital Universitario La Paz, Madrid
  5. 5Rheumatology Department, Hospital Universitario La Paz
  6. 6Rheumatology Department, Hospital Clinico San Carlos
  7. 7Rheumatology Department, Hospital Virgen de las Nieves
  8. 8Department of Biomedical Genetics, Complex Genetics Section, Utrecht University Medical Centre, Utrecht, The Netherlands
  1. Correspondence to:
    A Martínez
    Immunology Department, Hospital Clinico San Carlos, C/Martín Lagos, s/n, 28040 Madrid, Spain;alfmdoncel{at}terra.es

Abstract

Background: A Japanese study has described a strong association between rheumatoid arthritis and several polymorphisms located in the Fc receptor-like 3 (FCRL3) gene, a member of a family of genes related to Fc receptors located on chromosome 1q21–23.

Objectives: To evaluate the association between rheumatoid arthritis and FCLR3 polymorphisms in a large cohort of Caucasian patients with rheumatoid arthritis and healthy controls of Spanish origin. Owing to the described functional link between the FCRL3 polymorphisms and the transcription factor nuclear factor κB (NFκB), a functional polymorphism located in the NFκB1 gene was included.

Methods: 734 patients with rheumatoid arthritis from Madrid and Granada, Spain, were included in the study, along with 736 healthy controls. Polymorphisms in the FCRL3 gene were studied by TaqMan technology. The −94ins/delATTG NFκB1 promoter polymorphism was analysed by fragment analysis after polymerase chain reaction with labelled primers. Genotypes were compared using 3×2 contingency tables and χ2 values.

Results: No overall differences were found in any of the FCRL3 polymorphisms and in the NFκB1 promoter polymorphism when patients were compared with controls. However, when stratified according to NFκB1 genotypes, a susceptibility effect of FCRL3 polymorphisms was observed in patients who were heterozygotes for NFκB1 (pc = 0.003).

Conclusions: The FCRL3 polymorphisms associated with rheumatoid arthritis in a Japanese population are not associated per se with rheumatoid arthritis in a Spanish population. A genetic interaction was found between NFκB1 and FCRL3 in Spanish patients with rheumatoid arthritis. These findings may provide a general rationale for divergent genetic association results in different populations.

  • FCRL3, Fc receptor-like 3
  • HLA, human leucocyte antigen
  • NFκB, nuclear factor κB
  • SNP, single-nucleotide polymorphism

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Footnotes

  • Published Online First 13 February 2006

  • Funding: This work was supported by grant SAF03-3460 from Plan Nacional I+D+I.

  • Competing interests: AM is an employee with support from the “Fondo de Investigaciones Sanitarias” (CP04/00175). EU is a recipient of the “Ramon y Cajal” contract from the Spanish Science and Technology Ministry.

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