| Literature DB >> 18285546 |
Deborah French1, Leo H Hamilton, Leonard A Mattano, Harland N Sather, Meenakshi Devidas, James B Nachman, Mary V Relling.
Abstract
As glucocorticoid use increased in acute lymphoblastic leukemia, osteonecrosis became an increasingly frequent complication. Besides increased age, host risk factors are poorly defined. We tested whether 12 polymorphisms were associated with osteonecrosis among patients 10 years and older treated on the CCG1882 protocol. Candidate genes (TYMS, MTHFR, ABCB1, BGLAP, ACP5, LRP5, ESR1, PAI-1, VDR, PTH, and PTHR) were chosen based on putative mechanisms underlying osteonecrosis risk. All children received dexamethasone, with doses varying by treatment arm. A PAI-1 polymorphism (rs6092) was associated with risk of osteonecrosis in univariate (P = .002; odds ratio = 2.79) and multivariate (P = .002; odds ratio = 2.89) analyses (adjusting for gender, age, and treatment arm). Overall, 21 of 78 (26.9%) children with PAI-1 GA/AA genotypes, versus 25 of 214 (11.7%) children with GG genotype, developed osteonecrosis. PAI-1 polymorphisms and PAI-1 serum levels have previously been associated with thrombosis. We conclude that PAI-1 genetic variation may contribute to risk of osteonecrosis.Entities:
Mesh：
Substances：
Year: 2008 PMID： 18285546 PMCID： PMC2343589 DOI： 10.1182/blood-2007-11-123885
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113