Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjogren's syndrome
Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjogren's syndrome
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DOI：
10.1038/gene.2010.44
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发表时间：
2011-03-01
影响因子：
5
通讯作者：
Syvanen, A-C
中科院分区：
文献类型：
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作者：
Nordmark, G.;Kristjansdottir, G.;Syvanen, A-C
我们对来自瑞典（n = 344）和挪威（n = 196）的540例原发性干燥综合征（SS）患者和532例对照（n = 319瑞典人，n = 213挪威人）进行了候选基因关联研究。共分析了84个基因的1139个单核苷酸多态性（SNPs）。在瑞典和挪威队列的荟萃分析中，我们发现原发性SS和三个基因位点的SNP之间存在高信号关联，而这些基因位点以前与原发性SS无关。这些是早期B细胞因子1（EBF 1）基因，P = 9.9 × 10（-5），OR 1.68，具有序列相似性的167个成员的A-B淋巴酪氨酸激酶家族（FAM 167 A-BLK）基因座，P = 4.7 × 10（-4），OR 1.37和肿瘤坏死因子超家族（TNFSF 4 = Ox 40 L）基因，P = 7.4 × 10（-4），OR 1.34。我们还证实了原发性SS与IRF 5/TNPO 3基因座和STAT 4基因之间的关联。我们发现这五个基因的SNPs与抗SSA/抗SSB抗体的存在之间没有关联。EBF 1、BLK和TNFSF 4均参与B细胞的分化和活化，我们的结论是免疫系统中几个易感基因的多态性有助于原发性SS的发病。Genes and Immunity（2011）12，100-109; doi：10.1038/gene.2010.44; 2010年9月23日在线发表
We performed a candidate gene association study in 540 patients with primary Sjogren's Syndrome (SS) from Sweden (n = 344) and Norway (n = 196) and 532 controls (n = 319 Swedish, n = 213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P = 9.9 x 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P = 4.7 x 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4 = Ox40L) gene, P = 7.4 x 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS. Genes and Immunity (2011) 12, 100-109; doi:10.1038/gene.2010.44; published online 23 September 2010