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Series GSE11948 Query DataSets for GSE11948
Status Public on Sep 25, 2008
Title Bisphosphonate related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in MM
Organism Homo sapiens
Experiment type SNP genotyping by SNP array
Summary 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 two 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=1.07x10-6, p=4.231x10-6, p=6.22x10-6 and p=2.15x10-5, respectively). SNP rs1934951 was significantly associated with a higher risk of ONJ development even after Bonferroni correction (P corrected value=0.02). Genotyping results displayed an overrepresentation of the T allele in cases as 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 to 43.5).
Overall design We studied 22 cases (MM with ONJ) and 65 controls (MM without ONJ), matched for age, gender and ethnicity (note: all of the cases and controls are Caucasian). All patients were enrolled in the GEM-00 protocol, which consists on polychemotherapy and autologous transplantation. All received BPs therapy, either Pamidronate (16 cases, 57 controls) or Zoledronic Acid (6 cases, 8 controls) planned for 2 years (median 22 months, range 9-24 months). Clinical characteristics were similar between controls and cases. Study protocols were approved by the ethics committee and written informed consent was obtained from all participants.
Each patient was genotyped using the Affymetrix GeneChip Mapping 500K set of microarrays (Affymetrix, Santa Clara, CA) according to the manufacturer’s recommendations. Genotypes were determined using the BRLMM algorithm with cases and controls undergoing joint cluster analysis, after ensuring a robust association test through quality filtering tests. Based on stringent quality control criteria a total of 339.972 SNPs were selected for subsequent analyses. Criteria for exclusion were: 1) call rate<90%, 2) minor allele frequency <5% and 3) deviations from Hardy-Weinberg equilibrium with a p<0.00001. Sexual chromosomes were excluded for analysis.
To test for allelic associations between SNPs and ONJ, we constructed 2x2 contingency tables and compared using the two-sided Fisher’s exact or Chisquare tests through SPSS software (SPSS 14.0, Inc. Chicago, IL, USA). P-values were corrected (Pc) using the Bonferroni correction. The strength of association was estimated by the odds ratio (OR), and their 95% confidence intervals (CI) were calculated by Cornfield methods. Linkage disequilibrium between SNPs was analyzed using the Arlequin Software (
Contributor(s) Sarasquete ME, Garcia-Sanz R, Marin L, Alcoceba M, Chillon MC, Balanzategui A, Santamaria C, Rosiñol L, de la Rubia J, Hernandez MT, Garcia-Navarro I, Lahuerta JJ, Gonzalez M, San Miguel JF
Citation(s) 18594024
Submission date Jul 01, 2008
Last update date May 17, 2017
Contact name Maria Eugenia Sarasquete
Phone 0034-923-291629
Fax 0034-923-269066
Organization name Hospital Universitario de Salamanca
Department Hematology
Lab Molecular Biology
Street address Paseo San Vicente 58-182
City salamanca
State/province salamanca
ZIP/Postal code 37007
Country Spain
Platforms (2)
GPL3718 [Mapping250K_Nsp] Affymetrix Mapping 250K Nsp SNP Array
GPL3720 [Mapping250K_Sty] Affymetrix Mapping 250K Sty2 SNP Array
Samples (174)
BioProject PRJNA105805

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE11948_RAW.tar 4.3 Gb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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