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Title

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

AuthorsSarasquete, María Eugenia; García-Sanz, Ramón; Chillón, M. del Carmen; Santamaría, Carlos; Lahuerta, Juan José; González, Marcos ; San Miguel, Jesús F.
Issue Date2008
PublisherAmerican Society of Hematology
CitationBlood 112(7): 2709-2712 (2008)
AbstractWe 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 × 10-6, P= 4.231 × 10-6, P= 6.22 × 10-6, and P=2.15 × 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) © 2008 by The American Society of Hematology.
URIhttp://hdl.handle.net/10261/59545
DOI10.1182/blood-2008-04-147884
Identifiersdoi: 10.1182/blood-2008-04-147884
issn: 0006-4971
e-issn: 1528-0020
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