Cumulative Evidence for Associations Between Genetic Variants in Interleukin 6 Receptor Gene and Human Diseases and Phenotypes

作者全名："Zhang, Min; Bai, Ye; Wang, Yutong; Cui, Huijie; Tang, Mingshuang; Wang, Lanbing; Wang, Xin; Gu, Dongqing"

作者地址："[Zhang, Min; Bai, Ye] Chongqing Med Univ, Sch Publ Hlth & Management, Chongqing, Peoples R China; [Wang, Yutong; Cui, Huijie; Tang, Mingshuang; Wang, Xin] Sichuan Univ, West China Sch Publ Hlth, Dept Epidemiol & Med, Chengdu, Peoples R China; [Wang, Yutong; Cui, Huijie; Tang, Mingshuang; Wang, Xin] Sichuan Univ, West China Hosp 4, Chengdu, Peoples R China; [Wang, Lanbing] Army Mil Med Univ, Affiliated Hosp 1, Div Med Affairs, Chongqing, Peoples R China; [Gu, Dongqing] Army Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China"

通信作者："Gu, DA (通讯作者)，Army Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000796190600001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：interleukin 6 receptor; variant; cardiovascular diseases; inflammatory diseases; phenotypes

摘要："BackgroundGenetic studies have linked polymorphisms in the interleukin 6 receptor (IL6R) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize current knowledge of variants in the IL6R gene on the risk of diseases and phenotypes. MethodsWe searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence. ResultsWe included 155 studies for evaluating the associations between 80 polymorphisms in the IL6R gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn's disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions. ConclusionsOur study comprehensively summarizes current data on the genetic architecture of the IL6R gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases."

基金机构："National Natural Science Foundation of China [81903393, 81903398]"

基金资助正文："Funding This study was supported by the National Natural Science Foundation of China (81903393 and 81903398). The funding agencies of this study had no role in study design, data collection, data management, data analysis, data interpretation, writing of the manuscript, or the decision for submission."