Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific.
Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific.
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IL-6 与自身免疫性关节炎发展之间的遗传关联具有性别特异性
DOI：
10.3389/fimmu.2021.707617
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发表时间：
2021
影响因子：
7.3
通讯作者：
Yan S
中科院分区：
文献类型：
--
作者：
Hong J;Qu Z;Ji X;Li C;Zhang G;Jin C;Wang J;Zhang Y;Shen Y;Meng J;Zhou C;Fang C;Wang W;Yan S
目的探讨白细胞介素6（IL 6）与自身免疫性关节炎的遗传关系。方法我们使用多个全基因组关联研究（GWAS）数据集进行了双样本孟德尔随机化（MR）研究。此外，进行了性别分层MR研究，以确定IL 6和自身免疫性关节炎之间的关联性二态性。然后，基于IL 6 R基因区域显示LocusZoom图，以提供疾病之间遗传共定位的证据。结果MR结果显示IL-6信号水平升高与RA（β=0.325，95%CI 0.088，0.561，p=7.08E-03）和AS（β=1.240，95%CI 0.495，1.980，p=1.1E-03）的风险之间存在遗传相关性。相应地，发现sIL 6 R与RA（β=-0.020，95%CI-0.0320，-0.008，p =1.18E-03）和AS（β=-0.125，95%CI-0.177，-0.073，p =2.29E-06）的发病呈负相关。IL 6/sIL 6 R与PsA之间无遗传关联。性别分层MR分析显示，IL 6与男性人群中的AS相关，与女性人群中的RA相关，与男性人群中的PsA相关。此外，阿达尔（一种通过敏感性试验鉴定的基因）可能是合并人群中IL 6和PsA之间无显著关联的原因。结论IL-6信号通路过度激活导致自身免疫性关节炎的发生，尤其是在RA和AS中。在IL 6中间体对自身免疫性关节炎的易感性方面也观察到性别差异。
Objectives To find out the genetic association between IL6 and autoimmune arthritis. Methods We performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases. Results The MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (β=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (β=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (β=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (β=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population. Conclusion Our findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.
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影响因子：
168.9
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Duffy, David L.;Marks, Guy B.;Hui, Jennie;Le Souef, Peter;Danoy, Patrick;Baltic, Svetlana;Nyholt, Dale R.;Jenkins, Mark;Hayden, Catherine;Willemsen, Gonneke;Ang, Wei;Kuokkanen, Mikko;Beilby, John;Cheah, Faang;de Geus, Eco J. C.;Ramasamy, Adaikalavan;Vedantam, Sailaja;Salomaa, Veikko;Madden, Pamela A.;Heath, Andrew C.;Hopper, John L.;Visscher, Peter M.;Musk, Bill;Leeder, Stephen R.;Jarvelin, Marjo-Riitta;Pennell, Craig;Boomsma, Dorret I.;Hirschhorn, Joel N.;Walters, Haydn;Martin, Nicholas G.;James, Alan;Jones, Graham;Abramson, Michael J.;Robertson, Colin F.;Dharmage, Shyamali C.;Brown, Matthew A.;Montgomery, Grant W.;Thompson, Philip J.
通讯作者：
Thompson, Philip J.
DOI：
10.1155/2011/765624
发表时间：
2011
期刊：
Arthritis
影响因子：
--
作者：
Hashizume M;Mihara M
通讯作者：
Mihara M
影响因子：
16.6
作者：
Azizov, Vugar;Dietel, Katharina;Zaiss, Mario M.
通讯作者：
Zaiss, Mario M.
DOI：
10.1046/j.1432-1327.2001.01867.x
发表时间：
2001-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Jostock, T;Müllberg, J;Rose-John, S
通讯作者：
Rose-John, S
影响因子：
3.5
作者：
Hemani G;Bowden J;Davey Smith G
通讯作者：
Davey Smith G