Frequent co-occurrence of the TATA box mutation associated with Gilbert's syndrome (UGT1A1*28) with other polymorphisms of the UDP-glucuronosyltransferase-1 locus (UGT1A6*2 and UGT1A7*3) in Caucasians and Egyptians

被引:88
作者
Köhle, C
Möhrle, B
Münzel, PA
Schwab, M
Wernet, D
Badary, OA
Bock, KW [1 ]
机构
[1] Univ Tubingen, Inst Pharmacol & Toxicol, Tubingen, Germany
[2] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany
[3] Univ Hosp, Dept Transfus Med, Tubingen, Germany
[4] Al Azhar Univ, Dept Pharmacol & Toxicol, Coll Pharm, Cairo, Egypt
关键词
UGT1; polymorphisms; Gilbert's syndrome; genotype frequencies; haplotype frequencies;
D O I
10.1016/S0006-2952(03)00074-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Polymorphisms of drug metabolizing enzymes are frequently associated with diseases and side effects of drugs. Recently, a TATA box mutation of UGT1A1 (UGT1A1*28), a common genotype leading to Gilbert's syndrome, and several missense mutations of other UDP-glucuronosyltransferase 1 (UGT1) family members have been described. Furthermore, co-occurrence of UGT1A1*28 and UGT1A6*2 has been observed. In order to elucidate the basis for co-occurrence of UGT1 mutations, fluorescence resonance energy transfer techniques were developed for rapid determination of polymorphisms of three UGT isoforms (UGT1A1*28,1A6*2, and 1A7*2/*3). Hundred healthy Caucasians and 50 Egyptians were genotyped. All genotypes followed the Hardy-Weinberg equilibrium. Only three major haplotypes were found, including a haplotype consisting of allelic variants of all three isoforms (29% in Caucasians and 22% in Egyptians), all leading to reduced UGT activity. Frequent haplotypes containing several UGT1 allelic variants should be taken into account in studies on the association between diseases, abnormal drug reactions, and UGT1 family polymorphisms. (C) 2003 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:1521 / 1527
页数:7
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