Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Nov 2006; 65(11): 1538–1539.
PMCID: PMC1798348

Lack of association between signaling lymphocytic activation molecule family member 1 gene and rheumatoid arthritis in the French and Tunisian populations

Signaling lymphocytic activation molecule family member 1 (SLAMF1) is a member of the CD2 immunoglobulin superfamily, which is expressed in T cells, B cells, macrophages and dendritic cells.1SLAMF1 is associated with B cell proliferation and immunoglobulin synthesis.2 The expression of SLAMF1 in peripheral blood B cells from patients with rheumatoid arthritis was raised compared with healthy controls,3 and high expression of this molecule was observed in synovial fluid and tissue of patients with rheumatoid arthritis. Moreover, mice deficient in the SH2D1A molecule, which binds to the SLAMF1 receptor, were susceptible to experimental autoimmune diseases.4,5 Considering these biological data and the potential role of the SLAMF1 gene in regulating the immune system, we investigated the candidate gene SLAMF1 polymorphism, located on chromosome 1 (1q21.3–32.3), in patients with rheumatoid arthritis.

Three SLAMF1 single‐nucleotide polymorphisms were studied: C>A (rs 2295612) located in exon 1, G>C (rs 1809963) located in intron 4 and A>C (rs 3796504) located in exon 7. Firstly, 100 French patients with rheumatoid arthritis (87 women and 13 men; mean age: 32 years) in both parents were studied. Secondly, 103 Tunisian patients (85 women and 18 men; mean age: 50.7 years) and 111 healthy controls (64 women and 47 men; mean age: 54.8 years) were analysed in a case–control study. All patients selected fulfilled the 1987 American College of Rheumatology criteria for rheumatoid arthritis.6

The polymerase chain reaction‐restriction fragment length polymorphism technique was used for genotyping all samples (DdeI for rs2295612; BslI for rs1809963; Hpy188II for rs3796504; primer sequences and amplification programmes given on request).

Statistical analysis was examined by three different methods: transmission disequilibrium test, genotype relative risk and affected family‐based controls. Results from Tunisian control subjects and patients with rheumatoid arthritis were compared using the χ2 test and Fisher's exact test. SLAMF1 haplotypes in the French Caucasian trio and Tunisian population were inferred using Genehunter and Phase 2.1 softwares, respectively.

Allele frequencies for the three single‐nucleotide polymorphisms were in accordance with Hardy–Weinberg equilibrium in both Tunisian controls and French family‐based controls. Statistical analysis did not show any linkage disequilibrium between these markers in the Tunisian as well as in the French population (p>0.05). Transmission disequilibrium test analysis showed that rs2295612, rs1809963 and rs3796504 are not preferentially transmitted from heterozygotic parents to affected offsprings in the French trios with rheumatoid arthritis. Similar results were obtained using genotype relative risk and affected family‐based control tests (table 11).

Table thumbnail
Table 1 Analysis of the signalling lymphocytic activation molecule family member 1 single‐nucleotide polymorphisms by affected family‐based control, transmission disequilibrium and genotype relative risk tests in 100 French families ...

Moreover, our results showed the same distribution of SLAMF1 alleles and genotypes between Tunisian patients and controls (p>0.05).

Three different haplotypes (CCC, CCA, ACC) were identified at the SLAMF1 gene, with a frequency >5% in the French and Tunisian populations. Neither a significant disequilibrium of transmission to patients with rheumatoid arthritis nor a significant difference in distribution of these haplotypes between Tunisian patients with rheumatoid arthritis and controls was found.

Our study is the first report to examine the potential role of the SLAMF1 gene in the susceptibility to rheumatoid arthritis in both the French and Tunisian populations, which indicates that SLAMF1 polymorphisms do not contribute to susceptibility to rheumatoid arthritis in the studied populations. Our study should be replicated in other populations to confirm our preliminary results. Genotypes are available at http://www.GenHotel.com.

Acknowledgements

We sincerely appreciate the invaluable comments and encouragement of Professor Nadir Farid for his critical reading of the manuscript.

Footnotes

Funding: AFP, ARP, Association Française des Polyarthritiques, Association de Recherche pour la Polyarthrite, Association Polyarctique, SFR, Genopole (France), Ministère de l'Enseignement Supérieur, Ministère de la Recherche Scientifique et de la Technologie (Tunisa) and the International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste (Italy).

Competing interests: None declared.

References

1. Veillette A, Lattour S, Davidson D. Negative regulation of immunoreceptor signalling. Annu Rev Immunol 2002. 20669–707.707 [PubMed]
2. Punnonen J, Cooks B G, Carballido J M, Bennett B, Peterson D, Aversa G. et al Soluble and membrane‐bound forms of signaling lymphocytic activation molecule (SLAM) induce proliferation and Ig synthesis by activated human B lymphocytes. J Exp Med 1997. 185993–1004.1004 [PMC free article] [PubMed]
3. Isomaki P, Aversa G, Cooks B G, Luukkainen R, Saario R, Toivanen P. et al Increased expression of signalling lymphocytic activation molecule with rheumatoid arthritis and its role in the regulation of cytokine production in rheumatoid synovium. J Immunol 1997. 1592986–2993.2993 [PubMed]
4. Hron J D, Caplan L, Gerth A J, Schwartzberg P L, Peng S L. SH2D1A regulates T‐dependent humoral autoimmunity. J Exp Med 2004. 200261–266.266 [PMC free article] [PubMed]
5. Komori H, Furukawa H, Mori S, Ito M R, Terada M, Zhang M C. et al A signal adaptor SLAM‐associated protein regulates spontaneous autoimmunity and Fas‐dependent lymphoproliferation in MRL‐Faslpr lupus mice. J Immunol 2006. 176395–400.400 [PubMed]
6. Arnett F C, Edworthy S M, Bloch D A, McShane D J, Fries J F, Cooper N S. et al The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988. 31315–324.324 [PubMed]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...