遗传因素在广西新生儿高胆红素血症中的作用

目的探讨UGT1A1 G71R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％）,x^2=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．O％,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）L（44．80％）,X2=10．39,P=0．0013,前者发生高胆红素血症的伽（95％CT）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。

Role of genetic factors in occurrence of neonatal jaundice in Guangxi region

OBJECTIVE: To investigate the possible role of the UGT1A1 G71R or the OATP2 A388G genes mutation with coexisting G-6-PD deficiency in occurrence of neonatal hyperbilirubinemia. METHODS: Totally 109 umbilical cord blood samples were collected for the screening of G-6-PD activity by nitroblue tetrazolium (NBT) test and identification of G71R gene type by polymerase chain reaction combined with allele-specific oligonucleotide assay (ASO-PCR). At the same time, for 101 of the 109 cord blood samples A388G gene types were tested by restriction fragment length polymorphism (RFLP). According to G-6-PD activity and G71R or A388G genotype, the neonates were allocated into different groups. The authors compared the incidence rate of hyperbilirubinemia among different groups. Ten samples were sequenced to validate the results. RESULTS: Among the 109 umbilical cord blood specimens, the allele frequency of G71R was 22.03% in G-6-PD deficient group, 28.0% in G-6-PD normal group. The incidence rate of neonatal hyperbilirubinemia for those neonates who were G-6-PD deficient with coexisting homozygous or heterozygous variant of the G71R gene was significantly higher than that of neonates who were G-6-PD normal and had wild type G71R gene type, chi(2) = 10.45, P = 0.0012. The odds ratio (OR) of the former was 18.00 (95% CI: 2.12, 152.9). Among the 101 neonates, the allele frequency of A388G was 20.0% in G-6-PD deficient group and 18.5% in G-6-PD normal group. The incidence rate of neonatal hyperbilirubinemia for those neonates who were G-6-PD deficient with coexisting homozygous or heterozygous variant of the A388G gene was significantly higher than that of the neonates who were G-6-PD normal and had wild type A388G gene type, chi(2) = 10.39, P = 0.0013. The OR of the former was 11.8 (95% CI: 2.15, 56.48). CONCLUSION: G-6-PD deficiency coexists with G71R or A388G mutation in some individuals in Guangxi region. UGT1A1 G71R gene mutation combined with G-6-PD deficiency or A388G gene mutation combined with G-6-PD deficiency may play a coordinative role in the development of neonatal hyperbilirubinemia.