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
Copyright policy )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
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 (P=0.045), PON1 Q192R (P=0.039) and UGT1A6 T181A (P=0.025) 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% (P=0.05) 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.
- Kursk State Medical University Russian Federation
Adult, Epoxide Hydrolases, Male, Genotype, Aryldialkylphosphatase, Genetic Variation, Pilot Projects, Polymerase Chain Reaction, Asthma, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System, Risk Factors, Case-Control Studies, Cytochrome P-450 CYP1B1, Humans, Female, Genetic Predisposition to Disease, Aryl Hydrocarbon Hydroxylases, Glucuronosyltransferase, Polymorphism, Restriction Fragment Length
Adult, Epoxide Hydrolases, Male, Genotype, Aryldialkylphosphatase, Genetic Variation, Pilot Projects, Polymerase Chain Reaction, Asthma, Cytochrome P-450 CYP2D6, Cytochrome P-450 Enzyme System, Risk Factors, Case-Control Studies, Cytochrome P-450 CYP1B1, Humans, Female, Genetic Predisposition to Disease, Aryl Hydrocarbon Hydroxylases, Glucuronosyltransferase, Polymorphism, Restriction Fragment Length
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).36 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!