A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia:: a report from the Children's Oncology Group
A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia:: a report from the Children's Oncology Group
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DOI：
10.1182/blood-2007-11-123885
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发表时间：
2008-05-01
期刊：
影响因子：
20.3
通讯作者：
Relling, Mary V.
中科院分区：
文献类型：
--
作者：
French, Deborah;Hamilton, Leo H.;Relling, Mary V.
随着急性淋巴细胞性白血病糖皮质激素使用量的增加，骨坏死成为一种越来越常见的并发症。除了年龄增加外，宿主风险因素也没有明确的定义。我们测试了在接受CCG1882方案治疗的10岁及以上患者中，12个基因多态性是否与骨坏死有关。候选基因(Tyms、MTHFR、ABCB1、BGLAP、ACP5、LRP5、ESR1、PAI-1、VDR、PTH和PTHR)是根据可能的骨坏死风险机制选择的。所有儿童都接受了地塞米松治疗，剂量因治疗臂而异。在单变量(P=0.002；优势比=2.79)和多变量(P=0.002；优势比=2.89)分析(调整性别、年龄和治疗方法)中，PAI-1基因多态性(Rs6092)与骨坏死风险相关。总体而言，78名PAI-1 GA/AA基因型儿童中有21名(26.9%)发生骨坏死，而214名GG基因型儿童中有25名(11.7%)发生骨坏死。PAI-1基因多态性和PAI-1血清水平与血栓形成相关。我们得出结论，PAI-1基因变异可能与骨坏死的风险有关。
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.