CHRNA3 and CYP3A5*3 genotype, lung function and chronic obstructive pulmonary disease in the general population

Kaur-Knudsen, Diljit; Bojesen, Stig E.; Nordestgaard, Børge G.

doi:10.1097/fpc.0000000000000038

Cited by 5 publications

(2 citation statements)

References 23 publications

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“…We also confirmed the associations between this variance and incident COPD 4, 13, 14, tobacco‐related cancers 7, 15, 16, lung cancer 4, 7, 15, 17, 18, 19, 20, 21 and smoking quantity 2, 3, 7, indicating an exciting overlap of genetic influence on ND and smoking‐related diseases. As mentioned above, this region of the nAChRs is characterized by high correlation and the results should be interpreted as an association with the cluster instead of the rs1051730.…”

Section: Discussionsupporting

confidence: 74%

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

et al. 2015

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BackgroundGenetic variation in the cluster on chromosome 15, encoding the nicotinic acetylcholine receptor subunits (CHRNA5‐CHRNA3‐CHRNB4), has shown strong associations with tobacco consumption and an additional risk increase in smoking‐related diseases such as chronic obstructive pulmonary disease (COPD), peripheral artery disease and lung cancer.ObjectivesTo test whether rs1051730 (C/T), a tag for multiple variants in the CHRNA5‐CHRNA3‐CHRNB3 cluster, is associated with a change in risk of smoking‐related mortality and morbidity in the Malmö Diet and Cancer study, a population‐based prospective cohort study.MethodsAt baseline participants were classified as current (n = 6951), previous (n = 8426) or never (n = 9417) smokers. Cox‐proportional hazards models were used to determine the correlation between rs1051730 and incidence of first COPD, tobacco‐related cancer, other cancer and cardiovascular disease (CVD), and total mortality due to these causes, during approximately 14 years of follow‐up.ResultsAmongst current smokers there were 480 first incident COPD events, 852 tobacco‐related cancers, 810 other cancers and 1022 CVD events. A total of 1508 deaths occurred, including 500 due to CVD, 102 due to respiratory diseases and 677 due to cancer. In adjusted additive models, an increasing number of T alleles were associated with a gradual increase in total mortality, incident COPD and tobacco‐related cancer, even after adjustment for smoking quantity. No significant associations were observed amongst never smokers.ConclusionOur data suggest that gene variance in the CHRNA5‐CHRNA3‐CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco‐related cancer in smokers. These findings indicate an individual susceptibility to tobacco use and its complications; this may be important when targeting and designing smoking cessation therapies.

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Section: Discussionsupporting

confidence: 74%

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

et al. 2015

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“…[42] Based on the assumption that the activated PAHs are associated with decreased lung function, for which CYP3A5 is one of the PHA-metabolizing enzymes, [43][44][45] Kaur-Knudsen et al studied whether CYP3A5*3 influences lung function and the risk of chronic obstructive pulmonary disease (COPD) in smokers. [46] However, no association could be identified in the study between CYP3A5*3 and decreased lung function or risk of COPD among those who have smoked.…”

Section: Other Diseasesmentioning

confidence: 50%

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

Park

Jung

Kim

2014

Transl Clin Pharmacol

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The cytochrome P450 (CYP) 3A subfamily is estimated to participate in the biotransformation of 50% of the currently prescribed drugs. Four members of the CYP3A subfamily have been identified in humans: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. Initial data suggested that CYP3A5 accounts for only a small proportion of the total hepatic CYP3A in about 20% of samples, but it was later revealed that CYP3A5 represents more than 50% of the total CYP3A amount in some individuals. Several genetic variants have been described for the CYP3A5 gene, of which the CYP3A5*3 allele (gA6986G), the most common form and leading to the loss of CYP3A5 activity, has been extensively investigated in the aspect of pharmacokinetics and disease risk. This review summarized the molecular characteristics of the CYP3A5 gene, and discusses the association of the CYP3A5*3 polymorphism with disease risks such as cancer and hypertension, along with its role in the pharmacokinetics of CYP3A substrates.

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The early detection of asthma based on blood gene expression

Wang

Huang

2018

Mol Biol Rep

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CHRNA3 and CYP3A5*3 genotype, lung function and chronic obstructive pulmonary disease in the general population

Abstract: The CHRNA3 genotype is associated with decreased lung function and risk of COPD among ever-smokers, whereas this was not the case for CYP3A5*3.

Cited by 5 publications

References 23 publications

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role

The early detection of asthma based on blood gene expression

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CHRNA3 and CYP3A5*3 genotype, lung function and chronic obstructive pulmonary disease in the general population

Abstract: The CHRNA3 genotype is associated with decreased lung function and risk of COPD among ever-smokers, whereas this was not the case for CYP3A5*3.

Cited by 5 publications

References 23 publications

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

Gene variance in the nicotinic receptor cluster (CHRNA5‐CHRNA3‐CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers

CYP3A5*3Polymorphism and Its Clinical Implications and Pharmacokinetic Role

The early detection of asthma based on blood gene expression

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Product

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CYP3A5^3*Polymorphism and Its Clinical Implications and Pharmacokinetic Role