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Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis

Genes & Immunity volume 9, pages 214–223 (2008)Cite this article

A Corrigendum to this article was published on 22 October 2008

Abstract

Leukocyte immunoglobulin-like receptors (LILRs) are inhibitory, stimulatory or soluble receptors encoded within the leukocyte receptor complex. Some LILRs are extensively polymorphic, and exhibit evidence for balancing selection and association with disease susceptibility. LILRA2 (LIR7/ILT1) is an activating receptor highly expressed in inflammatory tissues, and is involved in granulocyte and macrophage activation. In this study, we examined the association of LILRA2 and adjacently located LILRA1 with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and microscopic polyangiitis (MPA). Polymorphism screening detected a LILRA2 SNP (rs2241524 G>A) that disrupts splice acceptor site of intron 6. Case–control association studies on 273 Japanese SLE, 296 RA, 50 MPA and 284 healthy individuals revealed increase of genotype A/A in SLE (12.1%, odds ratio (OR) 1.82, 95% confidence interval (CI) 1.02–3.24, P=0.041) and in MPA (16.0%, OR 2.52, 95% CI 1.07–5.96, P=0.049) compared with healthy individuals (7.0%). The risk allele caused an activation of a cryptic splice acceptor site that would lead to a novel LILRA2 isoform lacking three amino acids in the linker region (Δ419–421). Flow cytometry indicated that this isoform was expressed on the surface of monocytes. These findings suggested that LILRA2 Δ419–421 isoform encoded by the splice site SNP may play a role in SLE and MPA.

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Acknowledgements

We are indebted to Dr Jun Ohashi (The University of Tokyo) and Dr Ryosuke Kimura (Tokai University) for their helpful suggestions. Sequence accession number: The nucleotide sequence data reported in this paper have been submitted to the DDBJ database and have been assigned the accession numbers AB375279-AB375302. This work was supported by Grant-in-Aid for Scientific Research on Priority Areas ‘Applied Genomics’ from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS), grants from the Ministry of Health, Labour and Welfare of Japan, Takeda Science Foundation and Japan Rheumatism Foundation.

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Author notes

  1. K Mamegano and K Kuroki: These two authors equally contributed to this work.

Authors and Affiliations

  1. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    K Mamegano, R Miyashita & K Tokunaga

  2. Division of Structural Biol,

    K Kuroki & K Maenaka

  3. ogy, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    K Kuroki & K Maenaka

  4. Department of Rheumatology and Internal Medicine, Juntendo University, Tokyo, Japan

    M Kusaoi, S Kobayashi, H Hashimoto & Y Takasaki

  5. Matsuta Clinic, Tokyo, Japan

    K Matsuta

  6. Division of Biology and Bi,

    M Colonna

  7. omedical Science, Washington University, St Louis, MO, USA

    M Colonna

  8. Department of Internal Medicine, St Marianna University School of Medicine, Kawasaki, Japan

    S Ozaki

  9. Doctoral P,

    N Tsuchiya

  10. r,

    N Tsuchiya

  11. ogram in Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan

    N Tsuchiya

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  1. K Mamegano
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Correspondence to N Tsuchiya.

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Mamegano, K., Kuroki, K., Miyashita, R. et al. Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis. Genes Immun 9, 214–223 (2008). https://doi.org/10.1038/gene.2008.5

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