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 1).
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 with rheumatoid arthritis.
| SNP alleles | Allele frequencies | TDT | GRR | ||||
|---|---|---|---|---|---|---|---|
| Frequency transmitted | Frequency untransmitted | p Value | Transmitted | Untransmitted | p Value | p Value | |
| rs 2295612_C | 0.79 | 0.83 | 0.30 | 28 | 36 | 0.31 | 0.31 |
| rs 2295612_A | 0.21 | 0.17 | 36 | 28 | 0.31 | ||
| rs 1809963_C | 0.99 | 0.995 | 0.31 | 1 | 3 | 0.31 | 0.62 |
| rs 1809963_G | 0.01 | 0.005 | 3 | 1 | 0.31 | ||
| rs 3796504_C | 0.89 | 0.9 | 0.74 | 17 | 19 | 0.73 | 0.08 |
| rs 3796504_A | 0.11 | 0.1 | 19 | 17 | 0.73 | ||
GRR, genotype relative risk; SNP, single‐nucleotide polymorphism; TDT, transmission disequilibrium test.
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.
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