The Relationship Between UGT1A1、G6PD、GST Gene Polymorphisms And Neonatal Hyperbilirubinemia

Objective To investigate the characteristic of Uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) c.211G>A, Glucose-6-phosphate dehydrogenase(G6PD)c.1388G>A、c.1376G>T、c.95A >G and Glutathione s-transferase(GST)GSTT、、GSTM1 gene polymorphisms, and to explore the above gene polymorphisms and co-expression whether affect the development of neonatal hyperbilirubienmia.Methods1. A case-control study was performed, a total of 200 neonates were enrolled in the study, comprising 100 term hyperbilirubinemic neonates and 100 control subjects, applying polymerase chain reaction combine gene sequencing to detect the UGT1A1 gene c.211 G>A polymorphism, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect G6PD gene c.1388G>A、c.1376G>T、c.95A>G polymorphisms, multiplex polymorphism chain reaction to examine GST gene polymorphism, respectively.2. Compare the distribution of UGT1A1、G6PD and GST gene polymorphisms between hyperbilirubinemic group and control group, and explore the co-expression between the three examined gene polymorphisms and the development of neonatal hyperbilirubinemia.Results1. The homozygote (A/A) and heterozygote (A/G) of UGT1A1 gene c.211 G>A in hyperbilirubinemic group were 2 and 25, respectively, while in the control group, heterozygote were 2. The distribution of UGT1A1 c.211 G>A genotype had significant difference between the two groups (P<0.05). A allele frequency of UGTIA1 gene c.211G>A polymorphism in the hyperbilirubinemic group and control group were 0.145 and 0.075, respectively. There was a significant difference between the distribution of A allele frequency of UGTIA1 gene, and it was higher in hyperbilirubinemic group than in control group (χ2=5.001,P=0.025).2. The odds ratio and 95% confidence interval of UGT1A1 gene c.211G>A polymorphism was 2.096(1.036,4.239), P=0.040.3. There were 51 neonates (25.5%) with G6PD enzyme deficiency. The prevalence of G6PD of the case group (33.0%) was higher than eontrol group (18.0%), There was significant difference of the distribution between the case group and control group (x2=5.922, P=0.015); it was detected 34 neonates had G6PD gene mutation, the mutation frequency of G6PD gene of case group (27.0%) was higher than control group (7.0%) (x2=14.174, P=0.000). The frequency of G6PD c.1388G>A mutation of case group was higher than control group (χ2=6.438, P=0.011), the distribution of c.1376G>T and c.95A>G were no significant difference between the two groups (P>0.05); the total peak bilirubin of G6PD c.1388G>A, c.1376G>T and c.95A>G mutations had no significantly difference in case group (P>0.05)4. The OR and 95% CI of G6PD gene polymorphism was 4.914(2.026, 11.918), P=0.000.5. The neonates with GST gene GSTT1 and GSTM1 null genotype were 46 (46%) and 60 (60%) in case group respectively, along with control group of 45 (45%) and 53 (53%) respectively. The distribution of GSTT1 and GSTM1 null genotype had no significant difference between the two group (P >0.05).6. The OR and 95% CI of GST gene GSTT1, GSTM1 null mutation were 1.041(0.597,1.817),1.330(0.759,2.330), respectively, there were no significant difference between the two groups (P>0.05).7. Total peak bilirubin of UGT1A1 mutation genotype+G6PD mutation genotype、UGT1A1 mutation genotype+GST mutation genotype、G6PD mutation genotype+GST mutation genotype and UGT1A1 mutation genotype +G6PD mutation genotype+GST mutation genotype had no significant difference in case group (F=0.778, P=0.513); the OR and 95% CI of above gene mutations were 3.194(0.326,31.247)、1.633(0.778,3.429)、 1.888(0.891,3.999) and 2.020(0.180,22.645), respectively, there were no significant difference between them(P>0.05).Conclusions1. UGT1A1 gene c.211G>A polymorphism is detected as a risk factor in the development of neonatal hyperbilirubinemia.2. Of the three common mutation of G6PD, c.1388G>A mutation is the main genotype detected in the neonates, and the total peak bilirubin between G6PD c.1388G>A, c.1376G>T, c.95A>G mutations had no significantly difference in the detected neonates.3. GST gene GSTT1 and GSTM1 polymorphisms may not be a risk factor in development of neonatal hyperbilirubinemia in the detected neonates.4. The co-expression of UGTIA1、G6PD and GST gene polymorphisms may not be a risk factor in the development of neonatal hyperbilirubinemia.