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炎症性肠病和青少年特发性关节炎中的LACC1基因多态性

LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis.

作者信息

Assadi G, Saleh R, Hadizadeh F, Vesterlund L, Bonfiglio F, Halfvarson J, Törkvist L, Eriksson A S, Harris H E, Sundberg E, D'Amato M

机构信息

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.

Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.

出版信息

Genes Immun. 2016 Jun;17(4):261-4. doi: 10.1038/gene.2016.17. Epub 2016 Apr 21.

Abstract

The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).

摘要

含漆酶结构域1(LACC1)基因的功能尚不清楚,但据报道该基因座的遗传变异会持续影响克罗恩病(CD)和麻风病的发病风险。最近,在患有单基因形式CD以及系统性幼年特发性关节炎的患者中发现了LACC1错义突变。我们检验了这样一个假设,即除CD外,LACC1单核苷酸多态性(SNP)与幼年特发性关节炎(JIA,非系统性)以及另一种主要的炎症性肠病——溃疡性结肠炎(UC)有关。我们选择了11个LACC1标签SNP,并在来自CD、UC和JIA三个病例对照队列的3855名瑞典个体中测试了它们对疾病风险的影响。我们在所有三个队列中检测到经错误发现率校正后与单个标记的显著关联,从而将先前关于CD的结果扩展至UC和JIA。LACC1与多种炎症性疾病的关联表明其在人类免疫系统中起关键作用,并有理由对其功能进行进一步表征。

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