{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:27:50Z","timestamp":1792686470976,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>\n                    Medication\u2010related osteonecrosis of the jaw (MRONJ) is a rare but serious drug\u2010related adverse event. To identify pharmacogenomic markers of MRONJ associated with bisphosphonate therapy, we conducted a genomewide association study (GWAS) meta\u2010analysis followed by functional analysis of 5,008 individuals of European ancestry treated with bisphosphonates, which includes the largest number of MRONJ cases to date (444 cases and 4,564 controls). Discovery GWAS was performed in randomly selected 70% of the patients with cancer and replication GWAS was performed in the remaining 30% of the patients with cancer treated with intravenous bisphosphonates followed by meta\u2010analysis of all 3,639 patients with cancer. GWAS was also performed in 1,369 patients with osteoporosis treated with oral bisphosphonates. The lead single\u2010nucleotide polymorphism (SNP), rs2736308 on chromosome 8, was associated with an increased risk of MRONJ with an odds ratio (OR) of 2.71 and 95% confidence interval (CI) of 1.90\u20133.86 (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a03.57*10\n                    <jats:sup>\u22128<\/jats:sup>\n                    ) in the meta\u2010analysis of patients with cancer. This SNP was validated in the MRONJ GWAS in patients with osteoporosis (OR: 2.82, 95% CI: 1.55\u20134.09,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a06.84*10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). The meta\u2010analysis combining patients with cancer and patients with osteoporosis yielded the same lead SNP rs2736308 on chromosome 8 as the top SNP (OR: 2.74, 95% CI: 2.09\u20133.39,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a09.65*10\n                    <jats:sup>\u221211<\/jats:sup>\n                    ). This locus is associated with regulation of the\n                    <jats:italic>BLK<\/jats:italic>\n                    ,\n                    <jats:italic>CTSB<\/jats:italic>\n                    , and\n                    <jats:italic>FDFT1<\/jats:italic>\n                    genes, which had been associated with bone mineral density.\n                    <jats:italic>FDFT1<\/jats:italic>\n                    encodes a membrane\u2010associated enzyme, which is implicated in the bisphosphonate pathway. This study provides insights into the potential mechanism of MRONJ.\n                  <\/jats:p>","DOI":"10.1002\/cpt.2397","type":"journal-article","created":{"date-parts":[[2021,8,14]],"date-time":"2021-08-14T08:57:20Z","timestamp":1628931440000},"page":"1558-1569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genome\u2010wide Association Study Identified Chromosome 8 Locus Associated with Medication\u2010Related Osteonecrosis of the Jaw"],"prefix":"10.1111","volume":"110","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitrin W.","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jatinder K.","family":"Lamba","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"},{"name":"UF Health Cancer Center Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam","family":"Hamadeh","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"},{"name":"Cancer Pharmacology Department Levine Cancer Institute Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. Shannon","family":"Holliday","sequence":"additional","affiliation":[{"name":"Department of Orthodontics College of Dentistry University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine College of Pharmacy University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Oral Medicine College of Dentistry University of Florida Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Balla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos P.","family":"Kosa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Oncology Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Andrea","family":"Pelliccioni","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences \u2010 Section of Dentistry Alma Mater Studiorum\u2010Universit\u00e0 di Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas K.","family":"Price","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch National Cancer Institute Bethesda Maryland 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