title: Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis.
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 (Delta 419-421). Flow cytometry indicated that this isoform was expressed on the surface of monocytes. These findings suggested that LILRA2 Delta 419-421 isoform encoded by the splice site SNP may play a role in SLE and MPA.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mamegano
authors.forename: K
authors.initials: K
authors.lastname: Kuroki
authors.forename: R
authors.initials: R
authors.lastname: Miyashita
authors.forename: M
authors.initials: M
authors.lastname: Kusaoi
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Matsuta
authors.forename: K
authors.initials: K
authors.lastname: Maenaka
authors.forename: M
authors.initials: M
authors.lastname: Colonna
authors.forename: S
authors.initials: S
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Takasaki
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.forename: N
authors.initials: N
authors.lastname: Tsuchiya
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014657:Vasculitis / Q000235:genetics*
chemical_list: D017931:DNA Primers; C105298:LILRA2 protein, human; D011971:Receptors, Immunologic