Kim K, Cho S K, Han T U, Kim J H, Kang S J, Kang C, Bae S C
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Korea.
Lupus. 2013 Nov;22(13):1336-40. doi: 10.1177/0961203313504479. Epub 2013 Sep 6.
Two transcription factors in the type I interferon pathway, IRF5 and STAT4, have been genetically associated with susceptibility to both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to determine whether these two genes interact with each other to affect the disease susceptibilities.
The genetic interactions between IRF5 and STAT4 polymorphisms in SLE and RA susceptibility were examined using the epistasis options in PLINK software. This study analyzes the genetic data from 2558 unrelated Korean participants including 589 SLE patients, 987 RA patients, and 982 controls.
All 12 polymorphisms were individually associated with SLE susceptibility (p = 2.49 × 10(-8) to 0.00360). Among the three SLE-associated polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3-4) indel, exhibited the lowest p value (4.60 × 10(-5)) and accounted for the observed associations of the other two single-nucleotide polymorphisms (SNPs). Among the nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49 × 10(-8)) and accounted for all the other associations. These two polymorphisms, rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE susceptibility in a redundant manner (ORinteraction = 0.77, P epistasis = 0.040). Furthermore, these two polymorphisms, which had been individually associated with RA susceptibility, also interacted for RA susceptibility in the same manner (ORinteraction = 0.75, P epistasis = 0.014).
A redundant interaction between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling for further studies on confirmation of these findings.
I型干扰素通路中的两个转录因子，即IRF5和STAT4，在基因层面与系统性红斑狼疮（SLE）和类风湿关节炎（RA）的易感性相关。本研究旨在确定这两个基因是否相互作用以影响疾病易感性。
使用PLINK软件中的上位性选项，研究SLE和RA易感性中IRF5与STAT4基因多态性之间的遗传相互作用。本研究分析了2558名无亲缘关系的韩国参与者的遗传数据，包括589名SLE患者、987名RA患者和982名对照。
所有12种多态性均与SLE易感性单独相关（p = 2.49×10^(-8)至0.00360）。在IRF5的三种与SLE相关的多态性中，rs77571059，也称为CGGGG(3 - 4)插入缺失，表现出最低的p值（4.60×10^(-5)），并解释了其他两个单核苷酸多态性（SNP）的观察到的关联。在STAT4的九个与SLE相关的SNP中，rs16833215表现出最低的p值（2.49×10^(-8)），并解释了所有其他关联。IRF5的rs77571059和STAT4的rs16833215这两个多态性以冗余方式相互作用影响SLE易感性（OR相互作用 = 0.77，P上位性 = 0.040）。此外，这两个已分别与RA易感性相关的多态性，也以相同方式相互作用影响RA易感性（OR相互作用 = 0.75，P上位性 = 0.014）。
在I型干扰素通路相关的风湿性自身免疫疾病SLE和RA的易感性中，发现了IRF5和STAT4多态性之间的冗余相互作用，需要进一步研究以证实这些发现。
