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目的探讨UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏对在广西新生儿高胆红素血症发病的作用。方法用四氮唑蓝定量法(NBT法)测定G-6-PD酶活性。聚合酶链反应-等位基因特异性寡核苷酸探针点杂交(PCR-ASO)法确定G71R基因型。限制性片段长度多态性分析(RFLP)检测A388G基因型。测定109例新生儿脐血的G-6-PD活性及G71R基因型,其中101例同时检测了A388G基因型。据G-6-PD活性及G71R或A388G基因型分组,分析UGT1A1G71R突变、OATP2A388G突变和G-6-PD缺乏与足月新生儿高胆红素血症之间关系。结果G71R等位基因频率在G-6-PD缺乏组为22.03%,在G-6-PD正常组为28.00%。G-6-PD缺乏共存有G71R突变纯合子或杂合子的新生儿高胆红素血症发生率(95.50%)高于G-6-PD正常且G71R为野生型的新生儿(53.90%),χ2=10.45,P=0.0012,前者发生高胆红素血症的机会比(95%可信区间)[OR(95%CI)]为18.00(2.12,152.9)。A388G等位基因频率在G-6-PD缺乏组为20.0%,在G-6-PD正常组为18.5%。G-6-PD缺乏共存有A388G突变新生儿的高胆红素血症发生率(90.0%)高于G-6-PD正常且A388G为野生型的新生儿(44.80%),χ2=10.39,P=0.0013,前者发生高胆红素血症的OR(95%CI)为11.08(2.15,56.48)。结论G71R突变与G-6-PD缺乏共存或A388G突变与G-6-PD缺乏共存对广西足月新生儿高胆红素血症的发生有协同作用。
Objective To investigate the role of UGT1A1G71R mutation, OATP2A388G mutation and G-6-PD deficiency in the pathogenesis of neonatal hyperbilirubinemia in Guangxi. Methods G-6-PDase activity was determined by the method of tetrazolium blue (NBT method). G71R genotypes were determined by polymerase chain reaction-allele-specific oligonucleotide probe spot hybridization (PCR-ASO). A388G genotype was detected by restriction fragment length polymorphism (RFLP). G-6-PD activity and G71R genotypes were determined in 109 neonates with cord blood samples, of which 101 cases were also tested for the A388G genotype. The relationship between UGT1A1 G71R mutation, OATP2A388G mutation and G-6-PD deficiency and term neonatal hyperbilirubinemia was analyzed based on G-6-PD activity and G71R or A388G genotyping. Results The G71R allele frequency was 22.03% in G-6-PD deficient group and 28.00% in G-6-PD normal group. The incidence of neonatal hyperbilirubinemia (95.50%) in G-6-PD-deficient mice coexisting with G71R mutant homozygotes or heterozygotes was higher than that in normal neonates with G-6-PD and wild type G71R (53.90%) , χ2 = 10.45, P = 0.0012. The odds ratio (95% confidence interval) [OR (95% CI)] of the former with hyperbilirubinemia was 18.00 (2.12 and 152.9). The A388G allele frequency was 20.0% in the G-6-PD deficient group and 18.5% in the G-6-PD normal group. The incidence of hyperbilirubinemia (90.0%) in G-6-PD-deficient neonates with A388G mutation was higher than that in neonates with normal G-6-PD and A388G (44.80%), χ2 = 10.39, P = 0.0013, the former with hyperbilirubinemia OR (95% CI) was 11.08 (2.15,56.48). Conclusions The coexistence of G71R mutation and G-6-PD deficiency or the coexistence of A388G mutation and G-6-PD deficiency have a synergistic effect on the occurrence of hyperbilirubinemia in term full-term neonates of Guangxi.