Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren's syndrome
Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogren's syndrome
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DOI：
10.1038/gene.2008.94
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发表时间：
2009-01-01
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
原发性干燥综合征（SS）与系统性红斑狼疮（SLE）有许多共同特征。我们在瑞典和挪威原发性SS患者中研究了IRF 5和STAT 4三个主要多态性与SLE的相关性。这些多态性是IRF 5启动子中的5-bp CGGGG indel，IRF 5下游的单核苷酸多态性（SNP）rs 10488631和STAT 4 SNP rs7582694，其标记STAT 4的主要风险单倍型。我们观察到所有三种多态性与原发性SS之间的强相关信号，比值比（OR）> 1.4，P值< 0.01。我们还发现IRF 5和STAT 4的三个风险等位基因的强加性效应，风险等位基因的数量与原发性SS之间的总体显著性为P = 2.5 x 10（-9）。原发性SS的OR以累加方式增加，OR平均增加1.78。对于两个危险等位基因的携带者，原发性SS的OR为1.43，而五个危险等位基因的携带者的OR为6.78。IRF 5和STAT 4是I型IFN系统的组成部分，我们的研究结果强调了该系统在原发性SS发病机制中的重要性。
Primary Sjogren's syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) > 1.4 and P-values < 0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P = 2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.