udp -葡萄糖醛基转移酶1A1、1A6和1A8的功能多态性与慢性胰腺炎无关。

Mariette Verlaan, René H M te Morsche, Akos Pap, Robert J F Laheij, Jan B M J Jansen, Wilbert H M Peters, Joost P H Drenth
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引用次数: 17

摘要

目的:慢性胰腺炎(CP)与酗酒、吸烟和其他饮食或环境因素有关。udp -葡萄糖醛酸转移酶(UGTs)是II期解毒酶,负责各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变化的遗传变异具有毒理学和生理学意义,并且常常与疾病有关。我们研究了UGT1A1、UGT1A6和UGT1A8基因的多态性是否改变了CP的风险。方法:从258例酒精性CP患者(153例)、遗传性CP患者(25例)和特发性CP患者(80例)中获得DNA样本。对140名健康对照者的DNA进行分析比较。患者和对照组均为白种人。通过PCR测定ugt的遗传多态性,最后对所有受试者进行限制性片段长度多态性分析。结果:CP患者UGT1A1、UGT1A6和UGT1A8各等位基因的分布与健康对照组无显著差异。结论:这些数据提示UGT1A1、UGT1A6和UGT1A8基因多态性与白种人CP的发生无关。
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Functional polymorphisms of UDP-glucuronosyltransferases 1A1, 1A6 and 1A8 are not involved in chronic pancreatitis.

Objectives: 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.

Methods: 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.

Results: The distribution of the various alleles of UGT1A1, UGT1A6 and UGT1A8 did not differ between CP patients and healthy controls.

Conclusion: These data suggest that genetic polymorphisms in UGT1A1, UGT1A6 and in UGT1A8 do not predispose to the development of CP in Caucasians.

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