Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis
Association of LILRA2 (ILT1, LIR7) splice site polymorphism with systemic lupus erythematosus and microscopic polyangiitis
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DOI：
10.1038/gene.2008.5
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发表时间：
2008-04-01
影响因子：
5
通讯作者：
Tsuchiya, N.
中科院分区：
文献类型：
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作者：
Mamegano, K.;Kuroki, K.;Tsuchiya, N.
白细胞免疫球蛋白样受体（LILRs）是在白细胞受体复合体内编码的抑制性、刺激性或可溶性受体。一些lilr具有广泛的多态性，并显示出平衡选择和与疾病易感性相关的证据。LILRA2 （LIR7/ILT1）是炎症组织中高度表达的激活受体，参与粒细胞和巨噬细胞的活化。在这项研究中，我们研究了LILRA2和邻近位置的LILRA1与系统性红斑狼疮（SLE）、类风湿关节炎（RA）和显微镜下多血管炎（MPA）的关系。多态性筛选检测到LILRA2 SNP （rs2241524 G > a）破坏内含子6剪接受体位点。对273例日本SLE、296例RA、50例MPA和284例健康个体的病例对照研究显示，基因型A/A在SLE（12.1%，优势比（OR） 1.82, 95%可信区间（CI） 1.02 ~ 3.24， P=0.041）和MPA （16.0%, OR 2.52, 95% CI 1.07 ~ 5.96， P=0.049）中较健康个体（7.0%）增加。该风险等位基因激活了一个隐剪接受体位点，导致新的LILRA2异构体在连接区域缺少三个氨基酸（Delta 419-421）。流式细胞术显示该异构体在单核细胞表面表达。这些发现提示由剪接位点SNP编码的LILRA2 Delta 419-421异构体可能在SLE和MPA中发挥作用。
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.