GPA基因突变与慢性苯中毒的关系

目的探讨外周血红细胞血型糖蛋白A(glycophorin A,GPA)基因突变与慢性苯中毒的关系。方法用荧光标记单克隆抗体和流式细胞术,检测63名慢性苯中毒工人和45名同期接苯但无苯中毒表现的同工种对照工人外周血红细胞GPA基因突变频率。结果苯中毒组的白细胞、中性粒细胞计数明显低于对照组,差异有统计学意义(P<0.01);随着GPA-NN、GPA-Nφ突变频率增加,白细胞及中性粒细胞计数相应减少,两者间的趋势关系均有统计学意义(P<0.05)。GPA-NN突变频率随着累积接触评分增加而增加,两者间的趋势关系有统计学意义(P<0.05)。GPA-Nφ突变频率与累积接触评分间的趋势关系不明显(P>0.05)。结论苯中毒所表现的外周血白细胞、中性粒细胞数的降低,可能来源于骨髓干细胞的遗传损伤,即GPA-MN基因的纯合型(NN)基因突变。GPA-NN基因突变在慢性苯中毒的发病过程中起着重要作用。

Association of glycophorin A gene mutation in peripheral erythrocytes and chronic benzene poisoning

OBJECTIVE: To explore the association of the glycophorin A(GPA) gene mutation in peripheral erythrocytes and chronic benzene poisoning. METHODS: Sixty-three patients with chronic benzene poisonings and 45 benzene-exposed workers who were engaged in the same job title were investigated. Fluorescence immunolabeling technique and flowcytometry were used to detect GPA mutation frequency in peripheral read blood cell. RESULTS: A significant decrease in WBC count and neutrophil count was found in patients with chronic benzene poisoning compared with control individuals (P<0.01). The WBC count and neutrophil count both decreased along with the GPA-NN frequency, and the trends were significant(P<0.05).Both WBC counts and neutrophil counts decreased as the frequency, and trends were significant(P<0.05). GPA-NN frequency increased along with the accumulative exposure score, and the trend was significant (P = 0.0026). There was no significant trend between the GPA-Nphi frequency and the accumulative exposure score (P = 0.2037). CONCLUSION: A decrease in WBC count and neutrophil count is found in patients with chronic benzene poisoning, which can arise from genetic damage in bone marrow stem cells, namely gene-duplicating mutations (NN) at the GPA locus in bone marrow cells of MN-heterozygous subjects, GPA-NN mutagens contributed to the pathogenesis of chronic benzene poisoning.