Glutathione S-Transferase P1, Maternal Smoking, and Asthma in Children: A Haplotype-Based Analysis
نویسندگان
چکیده
BACKGROUND Glutathione S-transferase P1 (GSTP1) plays a role in a spectrum of respiratory diseases; however, the effects of sequence variation across the entire locus in asthma pathogenesis have yet to be determined. OBJECTIVES This study was designed to investigate whether sequence variations in the GSTP1 coding and promoter regions are associated with asthma and wheezing outcomes and to determine whether variants affect susceptibility to maternal smoking. METHODS Four haplotype tagging SNPs were selected that accounted for 83% of the common haplotypic variation in GSTP1. The associations of GSTP1 variants with asthma and wheezing were assessed among white children in the Children's Health Study (CHS). RESULTS The Ile105Val allele and a SNP in the upstream promoter region (SNP1: rs6591255, putative transcription factor 1 binding site) were associated with asthma and wheezing outcomes, an association observed in two cohorts of the CHS recruited in different years. Haplotypes that included both the promoter SNP (i.e., rs6591255) and the 105 Val variant were associated with an increased risk for asthma in non-Hispanic whites. Using SNP- and haplotype-based approaches, the effect of maternal smoking on wheezing was largest in children with the Ile105Val allele. CONCLUSIONS Variants in both the promoter and coding regions of the GSTP1 locus may contribute to the occurrence of childhood asthma and wheezing and may increase susceptibility to adverse effects of tobacco-smoke exposure.
منابع مشابه
Gst M1 and T1 Gene Variants Deficiency with Passive Maternal Smoking during Pregnancy May Increase Asthma Risk in Indian Children
It has been evident that Glutathione S-transferase (GST) gene deficiency may contribute to the development of asthma. Therefore, we aimed to assess the association of GSTT1 and GSTM1 deficiency with passive maternal smoking (MS) during pregnancy with asthma in north Indian children. It was a hospital based case-control study, 175 bronchial asthma cases and 175 controls, aged 1 year -15 years we...
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The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functions in pathways involved in asthma pathogenesis such as xenobiotic metabolism ...
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The association between glutathione S-transferase P1, M1 polymorphisms and asthma in Taiwanese schoolchildren.
STUDY OBJECTIVES Genetic polymorphisms in the glutathione S-transferase P1 gene (GSTP1) and the glutathione S-transferase M1 gene (GSTM1) have been implicated as risk factors for asthma. However, their roles in asthma pathogenesis and the interaction between these two genes have not been extensively investigated. This study, therefore, examined the relationship among GSTP1 and GSTM1 genotypes a...
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عنوان ژورنال:
دوره 116 شماره
صفحات -
تاریخ انتشار 2008