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谷胱甘肽硫转移酶 T1 和 M1 基因多态性作为北印度人群哮喘的主要危险因素。

GSTT1 and GSTM1 gene polymorphisms as major risk factors for asthma in a North Indian population.

机构信息

Department of Biotechnology, Panjab University, Chandigarh, India.

出版信息

Lung. 2012 Oct;190(5):505-12. doi: 10.1007/s00408-012-9385-9. Epub 2012 Apr 7.

Abstract

BACKGROUND

According to the National Family Health Survey, asthma is one of the leading diseases in India. In order to understand the complexity of asthma, the susceptibility genes need to be targeted for their association. Glutathione S-transferases play a major role in the detoxification of metabolites of oxidative stress resulting in inflammation and asthma. In the present study, the hypothesis that GSTT1 and GSTM1 gene polymorphisms are associated with asthma was examined.

METHODS

This is the first study to investigate the role of GSTT1 and GSTM1 gene polymorphisms in asthma pathogenesis in a North Indian population. A total of 824 subjects were recruited, of which 410 were asthma patients, including 323 patients suffering from allergic rhinitis. The other 414 recruits were healthy controls from regions of North India. Multiplex PCR was used for genotyping the GSTT1 and GSTM1 gene polymorphisms.

RESULTS

The GSTT1 null allele was more prevalent in asthma patients (40 %) than in the control subjects (13.3 %), which yielded a nearly fourfold risk towards asthma with odds ratio (OR) (95 % CI) = 4.35 (3.04-6.24), χ(2) = 75.34, and p = 0.000. The GSTM1 polymorphism also revealed a greater prevalence of the GSTM1 null allele in asthma patients (46.6 %) than in controls (39.4 %). Statistical analysis yielded a marginal risk toward asthma with OR (95 % CI) = 1.34 (1.01-1.79), χ(2) = 4.37, and p = 0.036.

CONCLUSIONS

Polymorphisms as a result of deletions in the GSTT1 and GSTM1 genes confer an increased risk towards asthma thereby suggesting the protective role of these functional genes in the development of the disease.

摘要

背景

根据全国家庭健康调查,哮喘是印度的主要疾病之一。为了了解哮喘的复杂性,需要针对其关联的易感基因进行靶向治疗。谷胱甘肽 S-转移酶在解毒氧化应激代谢物导致的炎症和哮喘中起主要作用。在本研究中,我们假设 GSTT1 和 GSTM1 基因多态性与哮喘有关。

方法

这是第一项研究,旨在调查 GSTT1 和 GSTM1 基因多态性在印度北部人群哮喘发病机制中的作用。共招募了 824 名受试者,其中 410 名是哮喘患者,包括 323 名患有过敏性鼻炎的患者。其余 414 名招募者来自印度北部地区的健康对照者。采用多重 PCR 技术对 GSTT1 和 GSTM1 基因多态性进行基因分型。

结果

哮喘患者 GSTT1 缺失等位基因(40%)比对照组(13.3%)更为常见,这使哮喘的风险增加了近四倍,比值比(OR)(95%可信区间)为 4.35(3.04-6.24),χ²=75.34,p=0.000。GSTM1 多态性也显示哮喘患者 GSTM1 缺失等位基因(46.6%)比对照组(39.4%)更为常见。统计分析显示哮喘的风险略有增加,OR(95%可信区间)为 1.34(1.01-1.79),χ²=4.37,p=0.036。

结论

GSTT1 和 GSTM1 基因缺失导致的多态性增加了哮喘的风险,这表明这些功能基因在疾病发展过程中具有保护作用。

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