McDougal Kathryn E, Fallin M Daniele, Moller David R, Song Zhimin, Cutler David J, Steiner Lori L, Cutting Garry R
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Invest Dermatol. 2009 Aug;129(8):1921-6. doi: 10.1038/jid.2008.456. Epub 2009 Feb 19.
Sarcoidosis is a multi-system inflammatory disease with organ involvement that varies by race and sex. Family studies indicate that genes play a role in the etiology and extent of organ involvement in sarcoidosis. In this study, we evaluated whether 25 variants distributed in 19 genes with a known role in inflammation were associated with erythema nodosum status in 659 sarcoidosis patients and 658 controls from A Case-Control Etiologic Study of Sarcoidosis (ACCESS). We found no association with affectation status; however, a variant in the promoter of tumor necrosis factor (TNF) at position -308 was found to be associated with erythema nodosum in Caucasian sarcoidosis patients (study-wide P=0.027). When separated by sex, a variant in intron 1 of lymphotoxin-alpha (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P=0.027). These DNA variants frequently occur together in Caucasians, and each variant has individually been associated with erythema nodosum in sarcoidosis patients. These results confirm that variation in the LTA/TNF gene cluster modifies a major skin manifestation of sarcoidosis and may explain the higher rate of erythema nodosum in females with sarcoidosis.
结节病是一种多系统炎症性疾病，其器官受累情况因种族和性别而异。家族研究表明，基因在结节病的病因及器官受累程度中起作用。在本研究中，我们评估了分布于19个在炎症中起已知作用的基因中的25个变异体，是否与结节病病例对照病因研究（ACCESS）中的659例结节病患者及658例对照的结节红斑状态相关。我们未发现与患病状态相关；然而，发现在白种人结节病患者中，肿瘤坏死因子（TNF）启动子-308位的一个变异体与结节红斑相关（全研究P=0.027）。按性别分开分析时，与TNF相邻的基因淋巴毒素-α（LTA）内含子1中的一个变异体，与白种人女性结节病患者的结节红斑相关（全研究P=0.027）。这些DNA变异体在白种人中经常共同出现，且每个变异体单独与结节病患者的结节红斑相关。这些结果证实，LTA/TNF基因簇的变异改变了结节病的一种主要皮肤表现，且可能解释了结节病女性中结节红斑发生率较高的原因。
