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稳定期男性 COPD 患者 GSTP1、GSTM1 和 GSTT1 基因多态性与血清 GST 总浓度

GSTP1, GSTM1 and GSTT1 genetic polymorphisms and total serum GST concentration in stable male COPD.

出版信息

Acta Pharm. 2014 Mar;64(1):117-29. doi: 10.2478/acph-2014-0003.

Abstract

The aim of this study was to test the hypothesis that glutathione- S-transferase (GST) genotypes were associated with COPD. GSTP1, GSTM1 and GSTT1 genotypes were determined by DNA methods and GST activity spectrophotometrically in older male Caucasian Croats (non- -smokers, ex-smokers, and smokers) with stable COPD (n = 30) and sex/age matched controls (n = 60). The distribution of GSTP1 genotypes and alleles in controls vs. COPD showed a statistical difference (p < 0.05). The odds ratio of CC/CT+TT (wild type GSTP1 exon 6 vs. joint heterozygous and mutant homozygous GSTP1 exon 6) was 10.000 and statistically different (p = 0.002). In this study, the GSTP1 mutant genotype of exon 5 (GG), as well as GSTP1 mutant and heterozygous genotypes of exon 6 (TT and CT), were suggested to be genetic contributors to COPD susceptibility. Null GSTM1, null GSTT1 and joint GSTM1/GSTT1 null genotypes were not disease associated. Serum GST was not associated with GST genotypes and COPD or smoking history in our study subjects. Conclusions drawn from the study should be further supported and clarified by studies with larger sample sizes.

摘要

本研究旨在验证谷胱甘肽-S-转移酶(GST)基因型与 COPD 相关的假设。采用 DNA 方法检测 GSTP1、GSTM1 和 GSTT1 基因型,并采用分光光度法检测老年高加索裔白人慢性阻塞性肺疾病(COPD)男性患者(非吸烟者、戒烟者和吸烟者,n = 30)和性别/年龄匹配对照者(n = 60)的 GST 活性。对照组与 COPD 组 GSTP1 基因型和等位基因的分布存在统计学差异(p < 0.05)。野生型 GSTP1 外显子 6(CC/CT+TT)的优势比为 10.000,差异具有统计学意义(p = 0.002)。在本研究中,exon5 的 GSTP1 突变基因型(GG)以及 exon6 的 GSTP1 突变和杂合基因型(TT 和 CT)被认为是 COPD 易感性的遗传因素。GSTM1 缺失型、GSTT1 缺失型和 GSTM1/GSTT1 联合缺失型与疾病无关。在我们的研究对象中,血清 GST 与 GST 基因型、COPD 或吸烟史均无相关性。本研究的结论应通过更大样本量的研究进一步支持和阐明。

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