易感基因-尿苷二磷酸葡萄糖醛酸基转移酶TATA盒突变与高胆红素血症及不随意运动型脑性瘫痪的相关性

Correlation between Mutation of Predisposing Genes-Uridine-Diphosphate-Glucucronosyl Transferase1A1 TATA Box and Morbility of Hyperbilirubinemia and Dyskinetic Cerebral Palsy

目的探讨易感基因-尿苷二磷酸葡萄糖醛酸基转移酶(UGT1A1)TATA盒的突变与高胆红素血症及不随意运动型脑性瘫痪(脑瘫)发病的相关性,为不随意运动型脑瘫的治疗提供理论根据。方法选取不随意运动型脑瘫41例(A组),高胆红素血症38例(B组),健康对照36例(C组)。分别抽取患儿及健康新生儿外周静脉血2mL,参照试剂盒说明分别提取其基因组DNA。应用聚合酶链反应(PCR)扩增UGT1A1基因,设计UGT1A1基因启动子TATA盒、引物序列,产物片段长度528bp。PCR产物纯化后直接测序找出相应的突变点。结果3组儿童孕龄、体质量、性别及喂养方式均无统计学差异(Pa>0.05);3组基因型分布有统计学差异(P<0.01)。A组41例患儿杂合子A(TA)6TAA/A(TA)7TAA型基因突变占36.6%,B组38例患儿(TA)6/7占15.8%,C组儿童无;而纯合子A(TA)7TAA/A(TA)7TAA型基因突变,A组占2.4%,B、C组均无;A组、B组基因型突变率明显高于C组,A组高于B组。结论易感基因-UGT1A1TATA盒突变与高胆红素血症及不随意运动型脑瘫具有明显相关。

Objective To study the correlation between the mutation of predisposing genes -uridine-diphosphate-glucucronosyl transferase1A1（UGT1A1） TATA box and the morbility of hyperbilirubinemia and dyskinetic cerebral palsy so as to explore the better theoretical foundation for the treatment of children with dyskinetic cerebral palsy.Methods Forty-one cases of dyskinetic cerebral palsy,38 cases of hyperbilirubinemia（group B） and 36 healthy newborn infants（group C） were selected.Peripheral vein blood samples were drawn from the newborn infants of each group,from which genomic DNA was extracted according to kit instructions,respectively.Polymerase chain reaction （PCR） was employed to amplify UGT1A1 gene.TATA box,the UGT1A1 gene promoter,and primer sequence were designed.The product fragment length of 528 bp was projected as well.Relevant mutational sites were found after directly sequencing the purified PCR products.Results There was no significant difference in gestational age,birth weight,gender and feeding patterns among group A,group B and group C（Pa0.05）.The genotype distribution among group A,group B,and group C had significant differences （P0.01）.Heterozygote[simplified （TA）6/7] type gene mutation accounted for 36.6% of all the 41 cases in group A,while [（TA）6/7] type gene mutation accounted for 15.8% of all the 38 cases in group B,and 0 in group C.Moreover,homozygote [simplified （TA）7/7] type gene mutation accounted for 2.4% in group A,and 0 in both group B and group C.The gene mutation rates in both group A and group B were higher than that in group C,and the rate in group A was higher than that in group B.Conclusion Apparent correlation exists between the mutation of predisposing genes-UGT1A1 TATA box and the morbility of hyperbilirubinemia and dyskinetic cerebral palsy.