Saadat Mostafa, Ansari-Lari Maryam
Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
Pak J Biol Sci. 2007 Dec 1;10(23):4183-9. doi: 10.3923/pjbs.2007.4183.4189.
Published studies have confirming or refusing an association between either glutathione S-transferase T1 (GSTT1) or M1 (GSTM1) polymorphism and asthma risk. Therefore the present meta-analysis was done. Literature-based meta-analysis was supplemented by tabular data from investigators of all relevant studies of two GST polymorphism (GSTM1 and GSTT1) available before May 2006, with investigation of potential sources of heterogeneity. Included in the resent study were 14 studies, involving a total 2292 asthma patients and 5718 controls. We found substantial evidence of heterogeneity between the studies. Exclusion of two studies with lowest quality scores resulted in a dramatic decrease in heterogeneity. The overall OR of the asthma risk associated with GSTM1 null genotype was 1.20 (95% CI: 1.08-1.35). Stratifying the meta-analysis by age and smoking status of subjects, the pooled ORs for GSTM1 null genotype were 1.56 (95% CI: 1.25-1.94) in adults and 1.95 (95% CI: 1.21-3.13) in non-smokers. The GSTT1 null genotype was associated with asthma risk in non-smoker adults (OR = 2.06, 95% CI: 1.21-3.71). To investigate whether profile of GST genotypes are associated with the risk of the asthma, further analysis combining the GSTT1 and GSTM1 genotypes were also carried out. Subjects with null genotypes for both GSTM1 and GSTT1 were at a significant higher risk for developing asthma (OR = 2.15, 95% CI: 1.39-3.33) compared with subjects who had both active genes. The trend in risk associated with zero, one and two putative high-risk genotypes was significant (chi2 = 12.07, df= 1, p = 0.0005). Overall, our present meta-analysis revealed that the null genotypes of GSTM1 and GSTT1 are associated with risk of asthma in adults especially in non-smoker ones. It might be suggested that chronic smoking carries such a high dose of toxins into the body that overloads the capacity of either GSTM1 or GSTT1 detoxification system. It seems that the GSTM1 and GSTT1 lack their protective values against development of asthma in adults with positive history of smoking. Present results also suggested that there is an additive effect for GSTT1 and GSTM1 genotypes.
已发表的研究证实或否定了谷胱甘肽S-转移酶T1（GSTT1）或M1（GSTM1）基因多态性与哮喘风险之间的关联。因此，进行了本次荟萃分析。基于文献的荟萃分析辅以2006年5月前所有关于两种GST基因多态性（GSTM1和GSTT1）的相关研究的研究者提供的表格数据，并调查了潜在的异质性来源。本研究纳入了14项研究，共涉及2292例哮喘患者和5718例对照。我们发现这些研究之间存在显著的异质性证据。排除两项质量得分最低的研究后，异质性显著降低。与GSTM1无效基因型相关的哮喘风险的总体比值比为1.20（95%可信区间：1.08 - 1.35）。根据受试者的年龄和吸烟状况对荟萃分析进行分层，GSTM1无效基因型在成年人中的合并比值比为1.56（95%可信区间：1.25 - 1.94），在非吸烟者中为1.95（95%可信区间：1.21 - 3.13）。GSTT1无效基因型与非吸烟成年人的哮喘风险相关（比值比 = 2.06，95%可信区间：1.21 - 3.71）。为了研究GST基因型谱是否与哮喘风险相关，还进行了将GSTT1和GSTM1基因型合并的进一步分析。与同时具有活性基因的受试者相比，GSTM1和GSTT1均为无效基因型的受试者患哮喘的风险显著更高（比值比 = 2.15，95%可信区间：1.39 - 3.33）。与零个、一个和两个假定的高风险基因型相关的风险趋势具有显著性（卡方 = 12.07，自由度 = 1，p = 0.0005）。总体而言，我们目前的荟萃分析表明，GSTM1和GSTT1的无效基因型与成年人尤其是非吸烟者的哮喘风险相关。可能是因为长期吸烟将如此高剂量的毒素带入体内，使GSTM1或GSTT1解毒系统的能力过载。似乎GSTM1和GSTT1对有吸烟史的成年人预防哮喘的发生缺乏保护作用。目前的结果还表明，GSTT1和GSTM1基因型存在相加效应。
