期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 39, 期 2, 页码 539-562出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyp337
关键词
Meta-analysis; systematic review; glutathione-S-transferase genes; GSTM1 gene; GSTT1 gene; GSTP1 gene; asthma; wheezing; bronchial responsiveness; The Avon Longitudinal Study of Parents and Children (ALSPAC)
资金
- UK Department of Health Policy Research Programme
- UK Medical Research Council
- Wellcome Trust
- University of Bristol
- British Lung Foundation
- Asthma, Allergy and Inflammation Research Trust
- Spanish Ministry of Health [FIS 97/0588, 00/0021-02, G03/176, PI06-1756]
- Medical Research Council [G9815508, G0902125, G0401540] Funding Source: researchfish
- MRC [G0401540, G0902125] Funding Source: UKRI
Methods Systematic review and meta-analysis of the effects of GST genes on asthma, wheezing and bronchial hyper-responsiveness (BHR), with inclusion of unpublished data from three studies, including the large Avon Longitudinal Study of Parents and Children (ALSPAC). Random effect or fixed effect models were used as appropriate, and sensitivity analyses were performed to assess the impact of study characteristics and quality on pooled results. Results The meta-analyses of GSTM1 (n = 22 studies) and GSTT1 (n = 19) showed increased asthma risk associated with the null genotype, but there was extreme between-study heterogeneity and publication bias and the association disappeared when meta-analysis was restricted to the largest studies. Meta-analysis of GSTP1 Ile105Val (n = 17) and asthma suggested a possible protective effect of the Val allele, but heterogeneity was extreme. Few studies evaluated wheezing and BHR and most reported no associations, although weak evidence was found for positive associations of GSTM1 null and GSTP1 Val allele with wheezing and a negative association of GSTP1 Val allele with BHR. Conclusions Our findings do not support a substantial role of GST genes alone in the development of asthma. Future studies of large size should focus on interactions of GST genes with environmental oxidative exposures and with other genes involved in antioxidant pathways. Quality of study conduct and reporting needs to be improved to increase credibility of the evidence accumulating over time.
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