中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2013年
4期
425-428
,共4页
孙顺昌%周指明%陈群蓉%彭运生%涂传清
孫順昌%週指明%陳群蓉%彭運生%塗傳清
손순창%주지명%진군용%팽운생%도전청
未结合型高胆红素血症%UGT1A1基因%突变分析
未結閤型高膽紅素血癥%UGT1A1基因%突變分析
미결합형고담홍소혈증%UGT1A1기인%돌변분석
Unconjugated hyperbilirubinemia%UGT1A1 gene%Mutation analysis
目的 分析未结合型高胆红素血症患者尿苷二磷酸葡糖醛酸基转移酶1A1(uridine diphosphate glucuronosyltransferase 1A1,UGT1A1)基因的突变情况,并探讨突变与血清总胆红素的关系.方法 抽提患者外周血基因组DNA,扩增UGT1A1基因的编码序列及启动子区,对扩增产物进行测序以确定基因突变.结果 在61例未结合型高胆红素血症患者中,共发现46例存在UGT1A1基因的突变.突变可分为5种,依据频率高低依次为211G→A、TATAA盒TA插入、686C→A、1091C→T以及1352C→T.携带单一位点纯合突变合并其它位点杂合突变患者的血清胆红素水平明显高于单位点纯合突变或多位点杂合突变患者(P<0.05).综合UGT1A1基因突变与血清总胆红素水平,44例未结合型高胆红素血症患者被诊断为Gilbert综合征,2例被诊断为Ⅱ型Crigler-Najjar综合征.结论 患者血清总胆红素水平不仅与UGT1A1基因突变数量有关,而且与突变的杂合或纯合状态有关.
目的 分析未結閤型高膽紅素血癥患者尿苷二燐痠葡糖醛痠基轉移酶1A1(uridine diphosphate glucuronosyltransferase 1A1,UGT1A1)基因的突變情況,併探討突變與血清總膽紅素的關繫.方法 抽提患者外週血基因組DNA,擴增UGT1A1基因的編碼序列及啟動子區,對擴增產物進行測序以確定基因突變.結果 在61例未結閤型高膽紅素血癥患者中,共髮現46例存在UGT1A1基因的突變.突變可分為5種,依據頻率高低依次為211G→A、TATAA盒TA插入、686C→A、1091C→T以及1352C→T.攜帶單一位點純閤突變閤併其它位點雜閤突變患者的血清膽紅素水平明顯高于單位點純閤突變或多位點雜閤突變患者(P<0.05).綜閤UGT1A1基因突變與血清總膽紅素水平,44例未結閤型高膽紅素血癥患者被診斷為Gilbert綜閤徵,2例被診斷為Ⅱ型Crigler-Najjar綜閤徵.結論 患者血清總膽紅素水平不僅與UGT1A1基因突變數量有關,而且與突變的雜閤或純閤狀態有關.
목적 분석미결합형고담홍소혈증환자뇨감이린산포당철산기전이매1A1(uridine diphosphate glucuronosyltransferase 1A1,UGT1A1)기인적돌변정황,병탐토돌변여혈청총담홍소적관계.방법 추제환자외주혈기인조DNA,확증UGT1A1기인적편마서렬급계동자구,대확증산물진행측서이학정기인돌변.결과 재61례미결합형고담홍소혈증환자중,공발현46례존재UGT1A1기인적돌변.돌변가분위5충,의거빈솔고저의차위211G→A、TATAA합TA삽입、686C→A、1091C→T이급1352C→T.휴대단일위점순합돌변합병기타위점잡합돌변환자적혈청담홍소수평명현고우단위점순합돌변혹다위점잡합돌변환자(P<0.05).종합UGT1A1기인돌변여혈청총담홍소수평,44례미결합형고담홍소혈증환자피진단위Gilbert종합정,2례피진단위Ⅱ형Crigler-Najjar종합정.결론 환자혈청총담홍소수평불부여UGT1A1기인돌변수량유관,이차여돌변적잡합혹순합상태유관.
Objective To analyze potential mutations of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1)gene in patients with unconjugated hyperbilirubinemia,and to explore the correlation between the mutations and total serum bilirubin levels.Methods Genomic DNA was extracted from peripheral blood samples of patients.Coding sequence and promoter region of the UGT1A1 gene were amplified.Mutations were identified through DNA sequencing.Results Mutations of the UGT1A1 gene were found in 46 out of 61 patients with unconjugated hyperbilirubinemia.Five types of mutations were detected,with a decreasing order of 211G→A,TA insertion in the TATAA promoter element,686C→,A,1091C→T and 1352C→T.Compared with those carrying a single homozygous mutation or compound heterozygous mutations,total serum bilirubin was higher in those carrying a homozygous mutation in combination with other heterozygous mutations (P< 0.05).Based on the UGT1A1 gene mutations and level of total serum bilirubin,44 patients were diagnosed with Gilbert syndrome,and 2 were diagnosed with Crigler-Najjar syndrome type 2.Conclusion The level of total serum bilirubin is correlated with the number of UGT1A1 gene mutations as well as their heterozygous or homozygous status.