Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Association Study of a Polymorphism of the CD244 Gene with Susceptibility to Systemic Lupus Erythematosus and with Clinical Features

Ota,  Yuko, Kawaguchi,  Yasushi, Kawamoto,  Manabu, Ikari,  Katsunori, Katsumata,  Yasuhiro, Gono,  Takahisa, Takagi,  Kae

Purpose:

CD244 belongs to a signaling lymphocyte activation molecule (SLAM) family and is expressed on all NK, ga, and memory CD8+ (ab) T cells. Recent findings on the molecular mechanisms of CD244 have indicated their important roles in the immune system in NK cells and T cells. It is possible that SLAM family proteins contribute to the development in autoimmune disorders, because a causal variant of a murine lupus model was identified in Ly108 gene, another member of the SLAM family. In human, a family-based association study of UK and Canadian families with systemic lupus erythematosus (SLE) revealed variants in the promoter and coding region of SLAMF7 and LY9, which were situated adjacent to CD244. The strongest association was detected in exon 8 of LY9. Those evidences suggest that CD244, one of the SLAM family, may be involved in disease susceptibility to SLE. Recently, it was reported that a single nucleotide polymorphisms (SNPs) in CD244 gene was significantly associated with susceptibility to RA. They did not replicate association of the LY9 gene with susceptibility to SLE in a Japanese population and very recent report did not replicate the association in 16 collections from 9 European countries, either. In the present study we explored the association of a single nucleotide polymorphism (SNP) of the CD244 gene with susceptibility to systemic lupus erythematosus (SLE) and with clinical manifestations of SLE in the Japanese population.

Method:

Two hundred forty-three patients with SLE and 756 healthy controls (HC) were enrolled in this study. Two SNPs (rs6682654 and rs3766379) in the CD244 gene were determined by allelic discrimination with the use of a specific TaqMan probe.

Results:

Only a SNP at rs3766379 of the CD244 gene was significantly associated with susceptibility to SLE (P = 0.023, odds ratio 1.3 [95% confidence interval 1.0–1.6]). The association was preferentially observed in subsets of SLE patients with nephritis and neuropsychiatric (NP)-lupus. The frequency of allele at rs6682654 was strongly associated with nephritis (P = 0.00065, odds ratio 2.0 [95% confidence interval 1.3–3.0]) and NP-lupus (P = 0.00000016, odds ratio 3.5 [95% confidence interval 2.1–5.7]), and the frequency of allele at rs3766379 was strongly associated with nephritis (P = 0.0014, odds ratio 1.9 [95% confidence interval 1.3–2.7]) and NP-lupus (P = 0.00000026, odds ratio 3.2 [95% confidence interval 2.0–5.0]).

Conclusion:

In this study, the CD244 gene was one of susceptibility-genes in patients with SLE. Especially, there was a strong association in SLE patients with nephritis and NP-lupus, suggesting that this genetic marker could predict the involvement of those severe complications.

To cite this abstract, please use the following information:
Ota, Yuko, Kawaguchi, Yasushi, Kawamoto, Manabu, Ikari, Katsunori, Katsumata, Yasuhiro, Gono, Takahisa, et al; Association Study of a Polymorphism of the CD244 Gene with Susceptibility to Systemic Lupus Erythematosus and with Clinical Features [abstract]. Arthritis Rheum 2009;60 Suppl 10 :110
DOI: 10.1002/art.25193

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