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Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis

التفاصيل البيبلوغرافية
العنوان: Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis
المؤلفون: Alonso Sarasquete, María Eugenia, García Sanz, Ramón, Marín Rubio, Luis Alberto, Alcoceba Sánchez, Miguel, Chillón Santos, María del Carmen, Balanzategui, A, Santamaria, Carlos, Rosiñol, Laura, De la Rubia, Javier, Hernandez, Miguel T., Garcia-Navarro, Inmaculada, Lahuerta, Juan José, González Díaz, Marcos, San Miguel Izquierdo, Jesús Fernando
بيانات النشر: American Society of Hematology
سنة النشر: 2008
المجموعة: Universidad de Salamanca: Gredos (Gestión del Repositorio Documental de la Universidad de Salamanca)
مصطلحات موضوعية: Bisphosphonate, Osteonecrosis of the Jaw, Myeloma, Genetic Polymorphisms, Genetic Predisposition to Disease, Diphosphonates, Jaw Diseases, Multiple Myeloma, Alleles, Haplotypes, Humans, Genome, Osteonecrosis, Aryl Hydrocarbon Hydroxylases, 3205.04 Hematología, alelos, difosfonatos, aril hidrocarburo hidroxilasas, humanos, enfermedades maxilomandibulares, mieloma múltiple, genoma, haplotipos, predisposición genética a la enfermedad
الوصف: Se trata de un descubrimiento de gran originalidad que liga la estructura del gen CYP2C8 y la fisiopatología dentaria como causa de osteonecrosis de mandíbula en pacientes bajo trata-miento con bisfosfonatos. Es uno de los verdaderos avances de la tecnología d SNPs en los denominados GWAS (Genomic Wide Association Studies, o estudios de asociación genética ampliada) ; [EN]We have explored the potential role of genetics in the development of osteonecrosis of the jaw (ONJ) in multiple myeloma (MM) patients under bisphosphonate therapy. A genome-wide association study was performed using 500 568 single nucleotide polymorphisms (SNPs) in 2 series of homogeneously treated MM patients, one with ONJ (22 MM cases) and another without ONJ (65 matched MM controls). Four SNPs (rs1934951, rs1934980, rs1341162, and rs17110453) mapped within the cytochrome P450-2C gene (CYP2C8) showed a different distribution between cases and controls with statistically significant differences (P = 1.07 x 10(-6), P = 4.231 x 10(-6), P = 6.22 x 10(-6), and P = 2.15 x 10(-6), respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value = .02). Genotyping results displayed an overrepresentation of the T allele in cases compared with controls (48% vs 12%). Thus, individuals homozygous for the T allele had an increased likelihood of developing ONJ (odds ratio 12.75, 95% confidence interval 3.7-43.5). ; Hospital Universitario de Salamanca Universidad de Salamanca ; Hospital Universitario de Salamanca
نوع الوثيقة: article in journal/newspaper
اللغة: English
تدمد: 0006-4971
1528-0020
العلاقة: https://doi.org/10.1182/blood-2008-04-147884Test; PI06-1354; Red Española de Cancer RD06/0020/0006; IDIBAPS; Sarasquete, M. E., García-Sanz, R., Marin, L., Alcoceba, M., Chillón, M. C., Balanzategui, A., . & San Miguel, J. F. (2008). Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood, The Journal of the American Society of Hematology, 112(7), 2709-2712. https://doi.org/10.1182/blood-2008-04-147884Test; http://hdl.handle.net/10366/155234Test
DOI: 10.1182/blood-2008-04-147884
الإتاحة: https://doi.org/10.1182/blood-2008-04-147884Test
http://hdl.handle.net/10366/155234Test
حقوق: Attribution-NonCommercial-NoDerivatives 4.0 Internacional ; http://creativecommons.org/licenses/by/4.0Test/ ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.92D9D305
قاعدة البيانات: BASE
الوصف
تدمد:00064971
15280020
DOI:10.1182/blood-2008-04-147884