Frontiers in Immunology (Aug 2018)
Genetic Regulation of the Thymic Stromal Lymphopoietin (TSLP)/TSLP Receptor (TSLPR) Gene Expression and Influence of Epistatic Interactions Between IL-33 and the TSLP/TSLPR Axis on Risk of Coronary Artery Disease
- Shao-Fang Nie,
- Shao-Fang Nie,
- Ling-Feng Zha,
- Ling-Feng Zha,
- Ling-Feng Zha,
- Qian Fan,
- Qian Fan,
- Qian Fan,
- Yu-Hua Liao,
- Yu-Hua Liao,
- Hong-Song Zhang,
- Hong-Song Zhang,
- Qian-Wen Chen,
- Qian-Wen Chen,
- Fan Wang,
- Ting-Ting Tang,
- Ting-Ting Tang,
- Ni Xia,
- Ni Xia,
- Cheng-Qi Xu,
- Jiao-Yue Zhang,
- Yu-Zhi Lu,
- Yu-Zhi Lu,
- Zhi-Peng Zeng,
- Zhi-Peng Zeng,
- Jiao Jiao,
- Jiao Jiao,
- Yuan-Yuan Li,
- Yuan-Yuan Li,
- Tian Xie,
- Tian Xie,
- Wen-Juan Zhang,
- Dan Wang,
- Chu-Chu Wang,
- Jing-Jing Fa,
- Hong-Bo Xiong,
- Jian Ye,
- Qing Yang,
- Peng-Yun Wang,
- Sheng-Hua Tian,
- Qiu-Lun Lv,
- Qing-Xian Li,
- Jin Qian,
- Bin Li,
- Gang Wu,
- Yan-Xia Wu,
- Yan Yang,
- Yan Yang,
- Xiang-Ping Yang,
- Yu Hu,
- Qing K. Wang,
- Xiang Cheng,
- Xiang Cheng,
- Xin Tu
Affiliations
- Shao-Fang Nie
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Shao-Fang Nie
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ling-Feng Zha
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ling-Feng Zha
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ling-Feng Zha
- Innovation Institute, Huazhong University of Science and Technology, Wuhan, China
- Qian Fan
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Fan
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian Fan
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China
- Yu-Hua Liao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yu-Hua Liao
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hong-Song Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hong-Song Zhang
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian-Wen Chen
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qian-Wen Chen
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Fan Wang
- Department of Molecular Cardiology, Cleveland Clinic Lerner Research Institute, Cleveland, OH, United States
- Ting-Ting Tang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ting-Ting Tang
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ni Xia
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Ni Xia
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Cheng-Qi Xu
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Jiao-Yue Zhang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yu-Zhi Lu
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yu-Zhi Lu
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zhi-Peng Zeng
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Zhi-Peng Zeng
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jiao Jiao
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Jiao Jiao
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuan-Yuan Li
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yuan-Yuan Li
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Tian Xie
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Tian Xie
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Wen-Juan Zhang
- Department of Geriatrics, the Central Hospital of Wuhan, Tongji Medica College, Huazhong University of Science and Technology, Wuhan, China
- Dan Wang
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Chu-Chu Wang
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Jing-Jing Fa
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Hong-Bo Xiong
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Jian Ye
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Qing Yang
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Peng-Yun Wang
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Sheng-Hua Tian
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qiu-Lun Lv
- Section of Molecule Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
- Qing-Xian Li
- 0Jining Medical College Affiliated Hospital, Jining, China
- Jin Qian
- 1Suizhou Central Hospital, Suizhou, China
- Bin Li
- 2Xiangyang Central Hospital, Xiangyang, China
- Gang Wu
- 3Renmin Hospital of Wuhan University, Wuhan, China
- Yan-Xia Wu
- 4Wuhan No. 1 Hospital, Wuhan, China
- Yan Yang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yan Yang
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Xiang-Ping Yang
- 5School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Yu Hu
- 6Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qing K. Wang
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- Xiang Cheng
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Xiang Cheng
- Key Laboratory for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Xin Tu
- Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China
- DOI
- https://doi.org/10.3389/fimmu.2018.01775
- Journal volume & issue
-
Vol. 9
Abstract
The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes TSLP, interleukin 7 receptor (IL7R), and TSLPR. Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933T in TSLP, Padj = 4.35 × 10−5, odds ratio (OR) = 1.18; rs6897932T in IL7R, Padj = 1.13 × 10−7, OR = 1.31; g.19646A>GA in TSLPR, Padj = 2.04 × 10−6, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence TSLP and IL7R expression, respectively. Furthermore, the “T” allele of rs3806933 might increase plasma TSLP levels (R2 = 0.175, P < 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant (Padj = 6.99 × 10−4, OR = 4.85). In addition, the epistatic interaction between TSLP and IL33 produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933TT-rs7025417TT (Padj = 3.67 × 10−4, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling.
Keywords
- thymic stromal lymphopoietin/TSLP receptor
- IL-33
- epistatic
- coronary artery disease
- genetic regulation
