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糖尿病患者的N-乙酰转移酶2基因多态性

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus.

作者信息

Yalin Serap, Hatungil Rezan, Tamer Lulufer, Ates Nurcan Aras, Dogruer Nil, Yildirim Hatice, Karakas Sevim, Atik Ugur

机构信息

Mersin University Pharmacy School, Department of Biochemistry, Mersin, Turkey.

出版信息

Cell Biochem Funct. 2007 Jul-Aug;25(4):407-11. doi: 10.1002/cbf.1314.

Abstract

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT25A, NAT26A, NAT27A/B and NAT214A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT25A and NAT26A mutant genotypes and NAT214A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 25A, OR = 18.48; 95%CI: 3.83-89.11 for NAT26A and OR = 18.22; 95%CI: 6.29-52.76 for NAT214A). However, the NAT27A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT26A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.

摘要

芳胺N - 乙酰基转移酶(NATs)是一类独特的酶家族,可催化乙酰辅酶A的乙酰基团转移至肼类、芳胺类药物及致癌物的末端氮原子上。已知人类芳胺NATs以两种同工酶NAT1和NAT2的形式存在。本研究的目的是确定NAT2的基因多态性是否在糖尿病(DM)易感性中起作用。本研究纳入了97例糖尿病患者和104例健康对照。使用罗氏诊断有限公司(德国曼海姆)的LightCycler实时PCR检测NAT25A、NAT26A、NAT27A/B和NAT214A多态性。根据我们的数据,NAT25A和NAT26A突变基因型以及NAT214A杂合基因型与糖尿病发生风险增加相关(NAT25A的OR = 47.06;95%CI:10.55 - 209.77,NAT26A的OR = 18.48;95%CI:3.83 - 89.11,NAT214A的OR = 18.22;95%CI:6.29 - 52.76)。然而,NAT27A/B基因多态性并未增加患糖尿病的风险。根据乙酰化表型分为慢乙酰化者或快乙酰化者后,发现NAT26A慢乙酰化者是糖尿病的一个显著风险因素(OR = 6.09;95%CI:1.99 - 18.6,p = 0.02)。结果表明,NAT2慢乙酰化者基因型可能是土耳其人群中糖尿病的一个重要遗传决定因素。

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