新生儿高未结合胆红素血症遗传因素的研究

目的：探讨尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）Gly71Arg、TATA盒基因突变和葡萄糖-6-磷酸脱氢酶（G6PD）基因突变与新生儿高未结合胆红素血症的关系。方法：UGT1A1 TATA盒、外显子1、外显子5和G6PD基因外显子12经PCR扩增和测序，构建突变样本的克隆，对其进行验证。分析病例组及对照组UGT1A1 Gly71Arg和TATA盒基因多态性频率的差异，应用logistic回归分析基因突变对新生儿高未结合胆红素血症发生的影响。结果：病例组UGT1A1 Gly71Arg基因多态性的基因型分布与对照组比较差异有统计学意义（P0.05）。Logistic回归分析显示UGT1A1 Gly71Arg、TATA盒基因和G6PD基因突变对新生儿高未结合胆红素血症发生的OR值（95％CI）分别为5.468（2.274，12.818）、0.688（0.266，1.778）和5.081（1.070，24.133）。结论：UGT1A1 Gly71Arg和G6PD基因突变可能是新生儿高未结合胆红素血症发生的原因。

Genetic factors in the occurrence of neonatal unconjugated hyperbilirubinemia

Objective To study association of uridine-diphosphate-glucuronosyltransferase1A1(UGT1A1) Gly71Arg,UGT1A1 promoter TATA-box and glucose-6-phosphate dehydrogenase(G6PD) gene mutations with the occurrence of neonatal unconjugated hyperbilirubinemia.Methods The TATA-box,exon 1 and exon 5 of the UGT1A1 gene and the exon 12 of G6PD gene were amplified by PCR.The products of PCR were analyzed by direct DNA sequencing.Clones for the mutations of the UGT1A1 gene and the G6PD gene were constructed in order to identify the results of the products of PCR.Seventy-two neonates with unconjugated hyperbilirubinemia(case group) and 65 healthy neonates(control group) were enrolled.The genotypes and allele frequencies of the polymorphisms of UGT1A1 Gly71Arg and UGT1A1 TATA-box were compared between the two groups.The effects of UGT1A1 Gly71Arg,UGT1A1 promoter TATA-box and G6PD gene mutations on the development of neonatal unconjugated hyperbilirubinemia were estimated using logistic regression models.Results There were significant differences in the genotype distribution of Gly71Arg polymorphism of UGT1A1 gene between the case and control groups(P<0.01).The Arg allele frequency of the polymorphisms of UGT1A1 gene in the case group was significantly higher than in the control group(P<0.01).There were no significant differences in the genotype distribution of the UGT1A1 promoter TATA-box between the two groups(P>0.05).The OR and 95%CI values of UGT1A1 Gly71Arg,UGT1A1 TATA-box and G6PD gene mutations associated with the development of neonatal unconjugated hyperbilirubinemia were 5.468(2.274,12.818),0.688(0.266,1.778) and 5.081(1.070,24.133) respectively.Conclusions UGT1A1 Gly71Arg and G6PD gene mutations may be involved in the development of neonatal unconjugated hyperbilirubinemia.