Verlaan Mariette, te Morsche René H M, Pap Akos, Laheij Robert J F, Jansen Jan B M J, Peters Wilbert H M, Drenth Joost P H
Department of Medicine, Division of Gastroenterology and Hepatology, University Medical Centre St Radboud, Nijmegen, The Netherlands.
Pharmacogenetics. 2004 Jun;14(6):351-7. doi: 10.1097/00008571-200406000-00004.
Chronic pancreatitis (CP) is associated with alcohol abuse, smoking and other dietary or environmental factors. UDP-glucuronosyltransferases (UGTs) are phase II detoxifying enzymes responsible for glucuronidation of various exogenous and endogenous compounds. Genetic variations, resulting in variable rates of glucuronidation, are of toxicological and physiological importance and are frequently associated with diseases. Recently, a genetic polymorphism in UGT1A7 was possibly associated with an increased risk for CP. We investigated whether polymorphisms in the genes for UGT1A1, UGT1A6 and UGT1A8 modified the risk for CP.
DNA samples were obtained from 258 adult CP patients with alcoholic (n = 153), hereditary (n = 25) or idiopathic (n = 80) origin. DNA from 140 healthy controls was analyzed for comparison. Patients and controls were all of Caucasian origin. Genetic polymorphisms in UGTs were determined by PCR, eventually followed by restriction-fragment-length-polymorphism analyses in all subjects.
The distribution of the various alleles of UGT1A1, UGT1A6 and UGT1A8 did not differ between CP patients and healthy controls.
These data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not predispose to the development of CP in Caucasians.
慢性胰腺炎(CP)与酗酒、吸烟以及其他饮食或环境因素相关。尿苷二磷酸葡萄糖醛酸基转移酶(UGTs)是Ⅱ期解毒酶,负责多种外源性和内源性化合物的葡萄糖醛酸化。导致葡萄糖醛酸化速率不同的基因变异具有毒理学和生理学重要性,且常与疾病相关。最近,UGT1A7基因的一个遗传多态性可能与CP风险增加有关。我们研究了UGT1A1、UGT1A6和UGT1A8基因的多态性是否会改变CP风险。
从258例成年CP患者获取DNA样本,这些患者病因分别为酒精性(n = 153)、遗传性(n = 25)或特发性(n = 80)。分析140例健康对照者的DNA用于比较。患者和对照者均为白种人。通过聚合酶链反应(PCR)确定UGTs的基因多态性,所有受试者最终进行限制性片段长度多态性分析。
UGT1A1、UGT1A6和UGT1A8各等位基因在CP患者和健康对照者中的分布无差异。
这些数据表明,UGT1A1、UGT1A6和UGT1A8的基因多态性不会使白种人易患CP。