A Functional Mutation in rs2664370 (T > C) in the 3'UTR of MMP16 Decreases the Risk of COPD Through Interactions with miR-576-5p: A Family and Population Based Study

The aberrant expression of Matrix Metalloproteinases (MMPs) is known to contribute to the pathogenesis of airway remodeling and alveolar disruption in chronic obstructive pulmonary diseases (COPD). This study explored the relationship between MMP genetic variants and the risk of COPD in family and population based studies. For the discovery stages, eleven COPD patients from five families were subjected to whole genome sequencing (WGS), and 21 common mutations in MMPs and TIMPs were identified. Of these mutations, two SNPs rs2664370 and rs2664369 in MMP16 remained significant differences (P C variant decreases the risk of COPD likely thorough increasing the interaction with hsa-miR-576-5p and reducing the expression of MMP16. Therefore, common mutations in MMP16 reduce COPD risk and improve plasma blood gas levels. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81520108001, 81700043, 81770043, and 81220108001), Guangdong Natural Science Foundation (2016A030313593), Guangzhou Science and Technology Programs for Science Study (201607020030), the National Key R&D Project (2016YFC 0903700), the 973 Key Scheme of China (2015CB553406), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2014, for WL), Guangdong Province Universities and Colleges Key Grant for Innovative Research (cxzd1142), Guangzhou Department of Education (1201620007, 13C08, and 12A001S), Open Project of State Key Laboratory of Respiratory Disease (SKLRD-OP-201808, SKLRD-QN-201719), Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program (2017BT01S155), and the National Key R&D Program of China (2018YFC1311900). Declaration of Interests: The authors declare: None. Ethics Approval Statement: The study was approved by the Institutional Review Board of Guangzhou Medical University (Ethics Committee of the First Affiliated Hospital (GZMC2009-08-1336)) and adhered to the Declaration of Helsinki as previously described.