Xin Xiong1, Duraid Hamied Naji1, Binbin Wang2, Yuanyuan Zhao1, Junhan Wang3, Dan Wang1, Yuting Zhang1, Sisi Li1, Shanshan Chen4, Yufeng Huang5, Qin Yang1, Xiaojing Wang1, Dan Yin1, Xin Tu1, Qiuyun Chen6, Xu Ma2, Chengqi Xu7, Qing K Wang8. 1. Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China. 2. National Research Institute for Family Planning, Beijing, China. 3. Department of Clinical Laboratory of University Hospital, Huazhong University of Science and Technology, Wuhan, China. 4. Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 6. Center for Cardiovascular Genetics, Cleveland Clinic, Cleveland, Ohio; Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. 7. Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China. Electronic address: cqxu@hust.edu.cn. 8. Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China; Center for Cardiovascular Genetics, Cleveland Clinic, Cleveland, Ohio; Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Department of Molecular Medicine, Case Western Reserve University, Cleveland, Ohio; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, Ohio. Electronic address: qkwang@hust.edu.cn.
Abstract
BACKGROUND: The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabetic patients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes. MATERIALS AND METHODS: We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls. RESULTS: rs3134069 showed significant association with ischemic stroke in the China-Central population (P = 9.24 × 10-3, odds ratio [OR] = 1.50). The association was replicated in the independent China-Northern population (P = 2.45 × 10-4, OR = 1.53). The association became more significant in the combined population (P = 7.09 × 10-6, OR = 1.41). The associations remained significant in the male population, female population, and population without type 2 diabetes. Our expression quantitative trait loci analysis found that the minor allele C of rs3134069 was significantly associated with a decreasedexpression level of TNFRSF11B (P = .002). CONCLUSIONS: This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.
BACKGROUND: The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabeticpatients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes. MATERIALS AND METHODS: We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls. RESULTS:rs3134069 showed significant association with ischemic stroke in the China-Central population (P = 9.24 × 10-3, odds ratio [OR] = 1.50). The association was replicated in the independent China-Northern population (P = 2.45 × 10-4, OR = 1.53). The association became more significant in the combined population (P = 7.09 × 10-6, OR = 1.41). The associations remained significant in the male population, female population, and population without type 2 diabetes. Our expression quantitative trait loci analysis found that the minor allele C of rs3134069 was significantly associated with a decreasedexpression level of TNFRSF11B (P = .002). CONCLUSIONS: This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.
Authors: Stephen A Bustin; Vladimir Benes; Jeremy A Garson; Jan Hellemans; Jim Huggett; Mikael Kubista; Reinhold Mueller; Tania Nolan; Michael W Pfaffl; Gregory L Shipley; Jo Vandesompele; Carl T Wittwer Journal: Clin Chem Date: 2009-02-26 Impact factor: 8.327
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Authors: Céline Bellenguez; Steve Bevan; Andreas Gschwendtner; Chris C A Spencer; Annette I Burgess; Matti Pirinen; Caroline A Jackson; Matthew Traylor; Amy Strange; Zhan Su; Gavin Band; Paul D Syme; Rainer Malik; Joanna Pera; Bo Norrving; Robin Lemmens; Colin Freeman; Renata Schanz; Tom James; Deborah Poole; Lee Murphy; Helen Segal; Lynelle Cortellini; Yu-Ching Cheng; Daniel Woo; Michael A Nalls; Bertram Müller-Myhsok; Christa Meisinger; Udo Seedorf; Helen Ross-Adams; Steven Boonen; Dorota Wloch-Kopec; Valerie Valant; Julia Slark; Karen Furie; Hossein Delavaran; Cordelia Langford; Panos Deloukas; Sarah Edkins; Sarah Hunt; Emma Gray; Serge Dronov; Leena Peltonen; Solveig Gretarsdottir; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Kari Stefansson; Giorgio B Boncoraglio; Eugenio A Parati; John Attia; Elizabeth Holliday; Chris Levi; Maria-Grazia Franzosi; Anuj Goel; Anna Helgadottir; Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Audrey Duncanson; Janusz Jankowski; Christopher G Mathew; Colin N A Palmer; Robert Plomin; Anna Rautanen; Stephen J Sawcer; Richard C Trembath; Ananth C Viswanathan; Nicholas W Wood; Bradford B Worrall; Steven J Kittner; Braxton D Mitchell; Brett Kissela; James F Meschia; Vincent Thijs; Arne Lindgren; Mary Joan Macleod; Agnieszka Slowik; Matthew Walters; Jonathan Rosand; Pankaj Sharma; Martin Farrall; Cathie L M Sudlow; Peter M Rothwell; Martin Dichgans; Peter Donnelly; Hugh S Markus Journal: Nat Genet Date: 2012-02-05 Impact factor: 38.330