Department of Dermatology, Institute of Clinical Medicine and Biomedicum Helsinki, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
PLoS One. 2010 Dec 2;5(12):e14212. doi: 10.1371/journal.pone.0014212.
Lupus erythematosus (LE) is a heterogeneous disease ranging from mainly skin-restricted manifestations (discoid LE [DLE] and subacute cutaneous LE) to a progressive multisystem disease (systemic LE [SLE]). Genetic association studies have recently identified several strong susceptibility genes for SLE, including integrin alpha M (ITGAM), also known as CD11b, whereas the genetic background of DLE is less clear.
To specifically investigate whether ITGAM is a susceptibility gene not only for SLE, but also for cutaneous DLE, we genotyped 177 patients with DLE, 85 patients with sporadic SLE, 190 index cases from SLE families and 395 population control individuals from Finland for nine genetic markers at the ITGAM locus. SLE patients were further subdivided by the presence or absence of discoid rash and renal involvement. In addition, 235 Finnish and Swedish patients positive for Ro/SSA-autoantibodies were included in a subphenotype analysis. Analysis of the ITGAM coding variant rs1143679 showed highly significant association to DLE in patients without signs of systemic disease (P-value = 4.73×10(-11), OR = 3.20, 95% CI = 2.23-4.57). Significant association was also detected to SLE patients (P-value = 8.29×10(-6), OR = 2.14, 95% CI = 1.52-3.00), and even stronger association was found when stratifying SLE patients by presence of discoid rash (P-value = 3.59×10(-8), OR = 3.76, 95% CI = 2.29-6.18).
We propose ITGAM as a novel susceptibility gene for cutaneous DLE. The risk effect is independent of systemic involvement and has an even stronger genetic influence on the risk of DLE than of SLE.
红斑狼疮（LE）是一种异质性疾病，范围从主要局限于皮肤的表现（盘状红斑狼疮[DLE]和亚急性皮肤红斑狼疮）到进行性多系统疾病（系统性红斑狼疮[SLE]）。遗传关联研究最近确定了几个 SLE 的强易感基因，包括整合素 alpha M（ITGAM），也称为 CD11b，而 DLE 的遗传背景则不太清楚。
为了专门研究 ITGAM 是否不仅是 SLE 的易感基因，也是皮肤 DLE 的易感基因，我们对 177 例 DLE 患者、85 例散发型 SLE 患者、190 例来自 SLE 家族的指数病例和 395 名来自芬兰的人群对照个体进行了 ITGAM 基因座上 9 个遗传标记的基因分型。SLE 患者根据有无盘状皮疹和肾脏受累进一步细分。此外，还对 235 例芬兰和瑞典的 Ro/SSA 自身抗体阳性患者进行了亚表型分析。对 ITGAM 编码变异 rs1143679 的分析显示，在无系统性疾病迹象的患者中，与 DLE 高度相关（P 值=4.73×10(-11)，OR=3.20，95%CI=2.23-4.57）。在 SLE 患者中也检测到显著相关性（P 值=8.29×10(-6)，OR=2.14，95%CI=1.52-3.00），当按是否存在盘状皮疹对 SLE 患者进行分层时，发现相关性更强（P 值=3.59×10(-8)，OR=3.76，95%CI=2.29-6.18）。
我们提出 ITGAM 是皮肤 DLE 的一个新的易感基因。这种风险效应独立于系统性受累，对 DLE 的遗传影响甚至比 SLE 更强。
