{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:56:19Z","timestamp":1787666179882,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173632"],"award-info":[{"award-number":["82173632"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202408110190"],"award-info":[{"award-number":["202408110190"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Drug\u2013gene interactions (DGIs) modify drug response and safety, yet their influence on diabetic microvascular complications remains unclear. This study aimed to elucidate the role of DGIs in these complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Using UK Biobank (UKB) data, we identified medications frequently prescribed to individuals with diabetes and defined DGIs based on the Food and Drug Administration (FDA) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Associations between DGIs and diabetic microvascular complications were evaluated using Cox proportional hazards models, which are suited for longitudinal time\u2010to\u2010event data. Two complementary analyses were performed: (1) a therapeutic class\u2010level analysis among medication users, and (2) a genotype\u2010level analysis among individuals with non\u2010normal metabolizer phenotypes who used the corresponding medications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 368 medications preferentially used among participants with diabetes, primarily cardiovascular agents and detected 55 clinically relevant DGIs implicating 30 medications and 7 genes. Among users of antithrombotic agents, the presence of DGIs was associated with diabetic kidney disease (DKD) (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.12\u20131.86) and diabetic neuropathy (DN) (HR: 2.13, 95% CI: 1.39\u20133.28). Likewise, among individuals with non\u2010normal metabolizer status for\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      or\n                      <jats:italic>CYP2D6<\/jats:italic>\n                      , DGIs conferred elevated risks for DKD and DN (HR range: 1.26\u20132.11). However, no significant association was found between DGI and DR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study provides the first comprehensive assessment of DGIs and diabetic microvascular complications. DGIs involving antithrombotic agents and non\u2010normal\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      or\n                      <jats:italic>CYP2D6<\/jats:italic>\n                      metabolizers were significantly linked to higher risks of DKD and DN. These findings underscore the potential of pharmacogenomic\u2010guided prescribing to enhance drug safety.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70501","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:06:17Z","timestamp":1769414777000},"page":"3115-3125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug\u2013gene interactions and the risk of diabetic microvascular complications: A population\u2010based cohort study"],"prefix":"10.1111","volume":"28","author":[{"given":"Ning","family":"Li","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Capital Medical University  Beijing China"},{"name":"Department of Statistics University of Auckland  Auckland New Zealand"},{"name":"Beijing Key Laboratory of environment and aging Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-2948","authenticated-orcid":false,"given":"Jiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Research Center, Beijing Chaoyang Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, O'Donnell School of Public Health University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Primary Health Care Research Lund University\/Region Sk\u00e5ne  Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medicinal Administration, Faculty of Health Sciences University of Macau  Macao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianmin","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Intelligent Diagnosis Technologies and Equipment for Optic Nerve\u2013Related Ocular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalu","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Statistics University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5659-5045","authenticated-orcid":false,"given":"Deqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, School of Public Health Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of environment and aging Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2017.12.005"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24\u20100011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397\u2010020\u20100162\u20105"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.12443"},{"key":"e_1_2_10_6_1","unstructured":"Administration UFaD.Table of pharmacogenetic associations. 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