title: 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.
abstract: 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).
authors.affiliation: Department of Haematology, Molecular Biology, and Human Leukocyte Antigen (HLA) Unit, University Hospital of Salamanca, Spain.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Sarasquete
authors.forename: Ramon
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Luis
authors.initials: L
authors.lastname: Marín
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.forename: Maria C
authors.initials: MC
authors.lastname: Chillón
authors.forename: Ana
authors.initials: A
authors.lastname: Balanzategui
authors.forename: Carlos
authors.initials: C
authors.lastname: Santamaria
authors.forename: Laura
authors.initials: L
authors.lastname: Rosiñol
authors.forename: Javier
authors.initials: J
authors.lastname: de la Rubia
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernandez
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Garcia-Navarro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Lahuerta
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065727:Cytochrome P-450 CYP2C8; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D010020:Osteonecrosis / Q000139:chemically induced / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D004164:Diphosphonates; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8