{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:50:32Z","timestamp":1789732232952,"version":"4.0.1"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T00:00:00Z","timestamp":1707523200000},"content-version":"vor","delay-in-days":2355,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Micromedic Inc, Israel"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,1,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole-exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta-analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single-nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case-control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome-wide association meta-analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01\u20130.46; p\u2009=\u20093.83\u2009\u00d7\u200910\u22125). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10\u20130.88), 0.26 (0.12\u20130.55), and 0.26 (0.12\u20130.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1\/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. \u00a9 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3285","type":"journal-article","created":{"date-parts":[[2017,8,31]],"date-time":"2017-08-31T11:34:12Z","timestamp":1504179252000},"page":"91-98","source":"Crossref","is-referenced-by-count":38,"title":["<i>SIRT1\/HERC4<\/i> Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis"],"prefix":"10.1093","volume":"33","author":[{"given":"Guang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issam S","family":"Hamadeh","sequence":"additional","affiliation":[{"name":"Cancer Pharmacology DepartmentLevine Cancer InstituteCharlotteNCUSA"},{"name":"Department of Pharmacotherapy and Translational Research and Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Katz","sequence":"additional","affiliation":[{"name":"Department of Oral MedicineCollege of DentistryUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Riva","sequence":"additional","affiliation":[{"name":"Bioinformatics CoreInterdisciplinary Center for Biotechnology ResearchUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lakatos","sequence":"additional","affiliation":[{"name":"1st Department of MedicineSemmelweis University Medical SchoolBudapestHungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadett","family":"Balla","sequence":"additional","affiliation":[{"name":"PentaCore LaboratoryBudapestHungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janos","family":"Kosa","sequence":"additional","affiliation":[{"name":"PentaCore LaboratoryBudapestHungary"},{"name":"1st Department of MedicineSemmelweis University Medical SchoolBudapestHungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaly","family":"Vaszilko","sequence":"additional","affiliation":[{"name":"Department of Oro-Maxillofacial Surgery and StomatologySemmelweis University Dental SchoolBudapestHungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Andrea","family":"Pelliccioni","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor SciencesSection of DentistryAlma Mater StudiorumUniversit\u00e0 di BolognaBolognaItaly"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Davis","sequence":"additional","affiliation":[{"name":"Micromedic Technologies Ltd.Tel AvivIsrael"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taimour Y","family":"Langaee","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan S","family":"Moreb","sequence":"additional","affiliation":[{"name":"Department of MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research and Center for PharmacogenomicsCollege of PharmacyUniversity of FloridaGainesvilleFLUSA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"issue":"9","key":"2024021014401639900_jbmr3285-bib-0001","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/S0278-2391(03)00720-1","article-title":"Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic","volume":"61","author":"Marx","year":"2003","journal-title":"J Oral Maxillofac Surg"},{"issue":"5","key":"2024021014401639900_jbmr3285-bib-0002","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.joms.2004.02.004","article-title":"Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases","volume":"62","author":"Ruggiero","year":"2004","journal-title":"J Oral Maxillofac Surg"},{"issue":"3","key":"2024021014401639900_jbmr3285-bib-0003","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.joms.2006.11.003","article-title":"Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws AeAoOaMS. 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