Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma
Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma
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DOI：
10.1111/j.1365-2222.2004.02099.x
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发表时间：
2004-11-01
影响因子：
6.1
通讯作者：
Guo, YL
中科院分区：
文献类型：
--
作者：
Lee, YL;Lin, YC;Guo, YL
谷胱甘肽s转移酶（GST） P1位点多态性与哮喘相关表型和支气管高反应性相关。目的探讨GSTP1基因型与室外空气污染是否为儿童哮喘的交互危险因素。方法选取台湾省南部3个空气污染程度不同的地区，共2853名四年级至九年级小学生，选取436名进行口腔黏膜采样。采用口腔黏膜DNA pcr检测GSTP1基因型。我们还进行了一项巢式病例对照研究，包括61名哮喘儿童和95名对照儿童，这些儿童经国际儿童哮喘和过敏研究问卷调查结果和甲胆碱激发试验证实。采用多元逻辑回归对潜在的混杂因素进行校正。结果所有参与者在Ala-114位点均为纯合子。虽然在不考虑空气污染的情况下，Ile-105基因座纯合子频率与哮喘之间仅存在微弱的显著相关性，但在调整混杂因素后，我们发现GSTP1-105等位基因与空气污染之间存在显著的基因-环境相互作用（P=0.035）。具体而言，我们发现与低污染地区携带任何Val-105等位基因的参与者相比，高污染地区携带Ile-105纯合子的参与者患哮喘的风险显著增加(调整优势比（AOR)=5.52, 95%置信区间(CI)=1.64-21.25）。与携带任何Val-105等位基因的儿童相比，在高污染区携带Ile-105纯合子的儿童患哮喘的风险显著增加（AOR=3.79, 95% CI=1.01 ~ 17.08），而在低污染区或中度污染区携带两个Ile-105等位基因的儿童患哮喘的风险不明显增加。携带Ile-105纯合子的儿童患哮喘的风险也与室外空气污染有明确的剂量-反应关系。结论GSTP1-105基因型与室外空气污染对儿童哮喘的影响存在基因-环境交互作用。
Background Polymorphisms at the glutathione S-transferase (GST) P1 locus were associated with asthma-related phenotypes and bronchial hyper-responsiveness.Objective This study investigated whether GSTP1 genotypes and outdoor air pollution were interactive risk factors on childhood asthma.Methods Four hundred and thirty-six subjects were recruited for oral mucosa samplings from 2853 fourth- to ninth-grade schoolchildren from three districts with different air pollution levels in southern Taiwan. PCR-based assays were performed by oral mucosa DNA to determine GSTP1 genotypes. We also conducted a nested case-control study comprising 61 asthmatic children and 95 controls confirmed by International Study of Asthma and Allergies in Childhood questionnaire results and methacholine challenge test. Multiple logistic regression was used to adjust for potential confounding factors.Results All participants were homozygous at the Ala-114 locus. Although only a marginally significant association existed between the frequency of homozygosity at the Ile-105 locus and asthma when air pollution was not considered, we found a significant gene-environmental interaction between GSTP1-105 alleles and air pollution after adjusting for confounders (P=0.035). Specifically, we found that compared with participants carrying any Val-105 allele in low air pollution, those who are Ile-105 homozygotes in high air pollution district had a significantly increased risk of asthma (adjusted odds ratio (AOR)=5.52, 95% confidence interval (CI)=1.64-21.25). Compared with participants carrying any Val-105 allele, in high air pollution district, children with Ile-105 homozygotes had a significantly increased risk of asthma (AOR=3.79, 95% CI=1.01-17.08), but those who carried two Ile-105 alleles in low or moderate air pollution districts did not show similar tendencies. The risk of asthma also revealed a clear dose-response relationship with outdoor air pollution in children with Ile-105 homozygotes.Conclusion Our result suggests a gene-environmental interaction between GSTP1-105 genotypes and outdoor air pollution on childhood asthma.