PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations

作者：Michael V. Holmes, Christiana Kartsonaki, Ruth Boxall, Kuang Lin, Nicola Reeve, Canqing Yu, Jun Lv, Derrick Bennett, Michael Hill, Ling Yang, Yiping Chen, Huaidong Du, Iain Turnbull, Rory Collins, Robert Clarke, Martin D. Tobin, Liming Li, Iona Y. Millwood, Zhengming Chen, Robin Walters, China Kadoorie Biobank Collaborative Group, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Guo Yu, Liming Li, Chen Wang, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Derrick Bennett, Ruth Boxall, Sushila Burgess, Ka Hung Chan, Yiping Chen, Zhengming Chen, Johnathan Clarke, Robert Clarke, Huaidong Du, Ahmed Edris, Hannah Fry, Simon Gilbert, Mike Hill, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, Mohsen Mazidi, Iona Y. Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Dan Schmidt, Paul Sherliker, Becky Stevens, Iain Turnbull, Robin Walters, Baihan Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Jun Lv, Pei Pei, Canqing Yu, Caixia Dong, Pengfei Ge, Xiaolan Ren, Zhongxiao Li, Enke Mao, Tao Wang, Hui Zhang, Xi Zhang, Jinyan Chen, Ximin Hu, Xiaohuan Wang, Zhendong Guo, Huimei Li, Yilei Li, Min Weng, Shukuan Wu, Shichun Yan, Mingyuan Zou, Xue Zhou, Ziyan Guo, Quan Kang, Yanjie Li, Bo Yu, Qinai Xu, Liang Chang, Lei Fan, Shixian Feng, Ding Zhang, Gang Zhou, Yulian Gao, Tian-You He, Pan He, Chen Hu, Huarong Sun, Xukui Zhang, Biyun Chen, Zhongxi Fu, Yuelong Huang, Huilin Liu, Qiaohua Xu, Yin Li, Huajun Long, Xin Xu, Hao Zhang, Libo Zhang, Naying Chen, Duo Liu, Zhenzhu Tang, Ningyu Chen, Qilian Jiang, Jian Lan, Mingqiang Li, Yun Liu, Fanwen Meng, Jinhuai Meng, Rong Pan, Yulu Qin, Ping Wang, Sisi Wang, Liuping Wei, Liyuan Zhou, Liang Cheng, Huaidong Du, Ruqin Gao, Feifei Li, Shanpeng Li, Yongmei Liu, Feng Ning, Zengchang Pang, Xiaohui Sun, Xiaocao Tian, Shaojie Wang, Yaoming Zhai, Hua Zhang, Wei Hou, Jun Lv, Junzheng Wang, Xiaofang Chen, Xianping Wu, Ningmei Zhang, Weiwei Zhou, Xiaofang Chen, Jianguo Li, Jiaqiu Liu, Guojin Luo, Qiang Sun, Xunfu Zhong, Jian Su, Ran Tao, Ming‐Fang Wu, Jie Yang, Jinyi Zhou, Yonglin Zhou, Yihe Hu, Yujie Hua, Jianrong Jin, Fang Liu, Jingchao Liu, Yan Lu, Liangcai Ma, Aiyu Tang, Jun Zhang, Weiwei Gong, Ruying Hu, Hao Wang, Meng Wang, Min Yu, Lingli Chen, Qijun Gu, Dongxia Pan, Chunmei Wang, Kaixu Xie, Xiaoyi Zhang · 发表于：European Journal of Preventive Cardiology · 年份：2024 · DOI：10.1093/eurjpc/zwae009 · 被引用次数：12 · 研究领域：Lipoproteins and Cardiovascular Health、Genetic Associations and Epidemiology、Genomics and Rare Diseases

AIMS: Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. METHODS AND RESULTS: In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45-0.83); P = 0.0015], major occlusive vascular events [n = 15 752; 0.80 (0.67-0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66-0.98); P = 0.029]. However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08-1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71-7.60); P = 7.3 × 10-4]. We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38-2.54); P = 5.4 × 10-5] and self-reported asthma [pooled OR of 1.17 (1.04-1.30...