Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus
Association of a single nucleotide polymorphism in the SH2D1A intronic region with systemic lupus erythematosus
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DOI：
10.1177/0961203313479421
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发表时间：
2013-04-01
期刊：
影响因子：
2.6
通讯作者：
Tohma, S.
中科院分区：
文献类型：
--
作者：
Furukawa, H.;Kawasaki, A.;Tohma, S.
SH 2D 1A，也称为信号淋巴细胞活化分子（SLAM）相关蛋白（SAP），是一种衔接蛋白。最近，有报道称SAP缺陷小鼠对系统性红斑狼疮（SLE）有保护作用。本研究假设SH 2D 1A基因是SLE的一个候选易感基因，并分析其与SLE的相关性。对506名日本女性SLE患者和330名健康女性对照的SH 2D 1A区域5个标签单核苷酸多态性（SNP）进行了病例对照关联研究。进行荧光素酶测定以确定与SLE相关的SNP的功能作用。内含子2中的一个SNP rs 2049995显示与SLE相关（p = 0.0110，优势比（OR）1.97，95%置信区间（CI）1.16-3.34，在显性模型下）。在发病年龄小于20岁的亚组中，rs 2049995的相关性似乎更强（p = 0.0067，OR 2.65，95% CI 1.28-5.46）。rs 2049995的功能评估表明，与抗性等位基因相比，易感等位基因的报告基因活性增加了1.9倍。SH 2D 1A的内含子SNP与SLE相关狼疮（2013）22，497-503。
SH2D1A, also known as signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), is an adaptor protein. Recently, it was reported that SAP deficient mice were protected from systemic lupus erythematosus (SLE). In this study, we postulated SH2D1A gene to be a candidate susceptibility gene for SLE and analyzed its association with SLE. A case-control association study was conducted on 5 tag single nucleotide polymorphisms (SNPs) in SH2D1A region in 506 Japanese female SLE patients and 330 healthy female controls. The luciferase assay was performed to determine the functional role of the SNP associated with SLE. One SNP in the intron 2, rs2049995, showed association with SLE (p = 0.0110, odds ratio (OR) 1.97, 95% confidence interval (CI) 1.16-3.34, under the dominant model). The association of rs2049995 seemed to be stronger in the subset with the age of onset less than 20 years (p = 0.0067, OR 2.65, 95% CI 1.28-5.46). Functional evaluation of rs2049995 showed that reporter gene activity was increased 1.9-fold for the susceptible allele compared with the resistant allele. An intronic SNP of SH2D1A is associated with SLE. Lupus (2013) 22, 497-503.