Bax griffle G(-248)A promoter polymorphism is associated with increased lifespan of the neutrophils of patients with osteomyelitis
Bax griffle G(-248)A promoter polymorphism is associated with increased lifespan of the neutrophils of patients with osteomyelitis
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DOI：
10.1097/gim.0b013e318039b23d
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发表时间：
2007-04-01
影响因子：
8.8
通讯作者：
Asensi, Victor
中科院分区：
文献类型：
--
作者：
Ocana, Marcos G.;Valle-Garay, Eulalia;Asensi, Victor
背景：骨髓炎患者外周血中性粒细胞自发凋亡率降低。bax基因启动子区的G（-248）A多态性与白血病患者外周血中性粒细胞存活时间延长相关，并可能在骨髓炎中发挥一定作用。研究方法：采用聚合酶链反应扩增Bax G（-248）A启动子，限制性片段长度多态性分析检测Bax G（-248）A启动子多态性。外周血中性粒细胞的自发性凋亡测定碘化丙啶，膜联蛋白V，流式细胞术，Bax蛋白质印迹法进行定量。结果如下：bax基因启动子多态性A等位基因在80例骨髓炎患者中的频率显著高于220例健康供体（18. 1% vs. 10.6%，chi（2）= 4.84，比值比= 1.81，95%可信区间= 1.06-3.07，P = 0.028）。A等位基因携带者外周血中性粒细胞凋亡率低于非携带者（33.3 +/- 16.7 vs. 43.1 +/- 3.1，P = 0.036）。与其他基因型携带者相比，AA基因型患者Bax蛋白表达较低（P = .038）。结论：bax基因-248位核苷酸G-A置换在骨髓炎患者中更常见，并与外周血中性粒细胞寿命延长和Bax蛋白表达降低相关。这些发现可能在骨髓炎的发病机制中发挥作用。
Background: Patients with osteomyelitis have a decreased rate of spontaneous apoptosis of their peripheral blood neutrophils. The G(-248)A polymorphism in the promoter region of the bax gene is associated with prolonged peripheral blood neutrophil survival in leukemic patients and may play some role in osteomyelitis. Methods: Bax G(-248)A promoter polymorphism was detected by DNA amplification using polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Spontaneous apoptosis of peripheral blood neutrophils was measured by propidium iodide, annexin V, and flow cytometry, and Bax was quantified by Western blotting. Results: The bax promoter polymorphism A allele was significantly more frequent in 80 patients with osteomyelitis than in 220 healthy donors (18.1% vs. 10.6%, chi(2) = 4.84, odds ratio = 1.81, 95% confidence interval = 1.06-3.07, P = .028). Carriers of the A allele had a lower apoptotic rate of their peripheral blood neutrophils compared with noncarriers (33.3 +/- 16.7 vs. 43.1 +/- 3.1, P = .036). Patients with the AA genotype showed a lower expression of the Bax protein compared with carriers of other genotypes (P = .038). Conclusions: Substitution of a nucleotide G-A at position -248 in the bax gene was more frequent in patients with osteomyelitis and was associated with a longer lifespan of their peripheral blood neutrophils and lower Bax protein expression. These findings may play a role in the pathogenesis of osteomyelitis.