Glutathione S-Transferase P1 Gene Polymorphism and Air Pollution as Interactive Risk Factors for Childhood Asthma

Lee, Yungling Leo; Lin, Ying‐Chu; Lee, Yeu-Chin; Wang, Jiu-Yao; Hsiue, Tzuen Ren; Guo, Yueliang Leon

doi:10.1097/00001648-200407000-00358

Cited by 40 publications

(57 citation statements)

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“…We also observed that individual responses to SHS and DEPs are correlated across the endpoints measured in this study. Our results provide further evidence that the severity of common allergic airway diseases, such as allergic rhinitis and asthma, is a consequence of the interplay between common genetic variants and environmental exposures (9,(35)(36)(37). The correlated responses to different exposures suggest that some individuals are at higher risk than others for…”

Section: Discussionsupporting

confidence: 54%

GlutathioneS-Transferases M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand Smoke

Gilliland

Gong

et al. 2006

Am J Respir Crit Care Med

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Rationale: Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize reactive oxygen species and detoxify electrophilic xenobiotics present in SHS and DEPs. Objectives: We tested the hypotheses that functional GSTM1-null genotype and GSTP1 codon 105 variants (Ile105 and Val105) are determinants of allergic responses to SHS, and that responses to SHS and DEPs are correlated. Methods and Measurements: In a randomized, placebo-controlled crossover trial, 19 ragweed allergen-sensitive subjects who had previously participated in a DEP trial were challenged intranasally with allergen after having been exposed to either clean air or SHS at separate visits. Nasal allergen-specific IgE, histamine, IL-4, and IFN-␥ levels were measured before and after allergen challenge. Main Results: Individuals with GSTM1-null or GSTP1 Ile105 genotypes showed larger nasal responses to allergens with SHS compared with clean air. GSTM1-null subjects had a larger increase in IgE than GSTM1-present subjects (median, 173.3 vs. 46.7 U/ml; p ϭ 0.03), and the Ile105 GSTP1 genotype subjects had increased histamine (median, 10.2 vs. 4.6 nM; p ϭ 0.01) after SHS plus allergen challenge. Responses to SHS and DEPs were correlated. Enhancement of IgE and histamine was greatest in the subjects with both the GSTM1-null and GSTP1 Ile/Ile genotypes. Conclusions: GSTM1 and GSTP1 are important cytoprotective factors that reduce SHS and DEP exacerbation of allergic responses.

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Section: Discussionsupporting

confidence: 54%

GlutathioneS-Transferases M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand Smoke

Gilliland

Gong

et al. 2006

Am J Respir Crit Care Med

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“…Therefore, gametic correlations between the disease-causing alleles, which occur specifically in asthmatics, may show an imbalance between toxification and detoxification processes, making such individuals more susceptible to environmental chemicals that are known to have a role in asthma etiology. 11,[14][15][16]18 It is important to notify that specific gametic correlations found between XME genes in asthmatics could be considered as a reflection of the disease-related patterns of genomic sequences responsible for the activation of cis-acting regulatory elements, such as xenobiotic responsive elements and antioxidant responsive elements. These DNA sequences are highly conserved in most XME families and are known to regulate the expression profiles of XMEs in response to chemicals.…”

Section: Discussionmentioning

confidence: 99%

“…8,10,12 Several genetic studies have observed that individuals possessing loss-of-function variants of genes for glutathione S-transferases (antioxidant enzymes) are more susceptible to adjuvant effects of airborne pollutants increasing the risk of bronchial asthma. 13,14 We have recently confirmed that some other antioxidant genes are also proper candidates for asthma susceptibility genes. [15][16][17][18] However, a little research has been conducted to investigate the impact of highly variable polymorphic genes for xenobiotic-metabolizing enzymes (XMEs) on the development of bronchial asthma.…”

Section: Introductionmentioning

confidence: 93%

Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: the importance of gene–gene and gene–environment interactions for disease susceptibility

2009

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The aim of our pilot study was to evaluate the contribution of genes for xenobiotic-metabolizing enzymes (XMEs) for the development of bronchial asthma. We have genotyped 25 polymorphic variants of 18 key XME genes in 429 Russians, including 215 asthmatics and 214 healthy controls by a polymerase chain reaction, followed by restriction fragment length polymorphism analyses. We found for the first time significant associations of CYP1B1 V432L (P¼0.045), PON1 Q192R (P¼0.039) and UGT1A6 T181A (P¼0.025) gene polymorphisms with asthma susceptibility. Significant P-values were evaluated through Monte-Carlo simulations. The multifactor-dimensionality reduction method has obtained the best three-locus model for gene-gene interactions between three loci, EPHX1 Y113H, CYP1B1 V432L and CYP2D6 G1934A, in asthma at a maximum cross-validation consistency of 100% (P¼0.05) and a minimum prediction error of 37.8%. We revealed statistically significant gene-environment interactions (XME genotypes-smoking interactions) responsible for asthma susceptibility for seven XME genes. A specific pattern of gametic correlations between alleles of XME genes was found in asthmatics in comparison with healthy individuals. The study results point to the potential relevance of toxicogenomic mechanisms of bronchial asthma in the modern world, and may thereby provide a novel direction in the genetic research of the respiratory disease in the future.

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“…For example, the Val105 allele decreased the risk of asthma in Northern Europeans for which the Val allele frequency is 47.7% (12), whereas the Val105 allele increased the risk of asthma in the Japanese population for which the Val allele frequency is 13.4% (14). Studies in Taiwanese individuals (Val allele frequencys25.3%) (15) have shown that the Ile105 homozygosity was related to an increased risk only in areas with high air pollution, and no association was found in areas with low air pollution. These data suggest that the role of GSTP Ile105Val polymorphisms in the risk of AD could differ depending on ethnicity.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, homozygous deletion of the GSTM1 and GSTT1 genes leads to the absence of the GSTM1 and GSTT1 proteins and their activity resulting in a null phenotype (11). Previous studies have reported an association between GST polymorphisms and an increased risk of inflammatory diseases such as asthma (12)(13)(14)(15)(16) and rheumatoid arthritis (17). A limited number of studies have examined the association of GST polymorphisms with risk of AD; the findings have been inconclusive (18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

Chung

Shin

2009

Clinical Chemistry and Laboratory Medicine

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Background: Glutathione S-transferase (GST) enzymes are critical for detoxifying reactive oxygen species (ROS) and their products which have been implicated in the pathology of inflammatory diseases such as atopic dermatitis (AD). Methods:We investigated the effects of genetic polymorphisms of GST on the risk of AD in preschool age children. Biomarkers for oxidative stress were also evaluated with respect to GST genotype. Results: The GSTP1 Val105 allele was significantly associated with an increased risk of AD wodds ratio (OR)s1.62, p-0.05x. The combination of the GSTP1 Val105 allele and the GSTT1 null genotype further increased this risk by 2.3-fold (p-0.01). No association was observed for the GSTM1 null or GSTT1 null genotype alone. In children with AD, blood total antioxidant capacity was significantly less (p-0.001), while malondialdehyde was higher (ps0.12). Children with the GSTP1 Val105 allele had significantly lower concentrations of erythrocyte glutathione compared to GSTP1 Ile/Ile homozygotes (ps0.03). Conclusions: Our study suggests that the GSTP1 Val105 allele is an important determinant of susceptibility to AD in preschool age children and increased oxidative stress may play a role in the pathogenesis of AD.

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Glutathione S-Transferase P1 Gene Polymorphism and Air Pollution as Interactive Risk Factors for Childhood Asthma

Cited by 40 publications

References 0 publications

GlutathioneS-Transferases M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand Smoke

GlutathioneS-Transferases M1 and P1 Prevent Aggravation of Allergic Responses by Secondhand Smoke

Genetic variation of genes for xenobiotic-metabolizing enzymes and risk of bronchial asthma: the importance of gene–gene and gene–environment interactions for disease susceptibility

Association of glutathione-S-transferase polymorphisms with atopic dermatitis risk in preschool age children

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