Bax gene G(-248)A promoter polymorphism is associated with increased lifespan of the neutrophils of patients with osteomyelitis

Abstract

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=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.