Back to Search
Start Over
Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms.
- Source :
-
Human molecular genetics [Hum Mol Genet] 2014 Jan 15; Vol. 23 (2), pp. 555-61. Date of Electronic Publication: 2013 Sep 17. - Publication Year :
- 2014
-
Abstract
- Genome-wide significant associations with cigarettes per day (CPD) and risk for lung cancer and chronic obstructive pulmonary disease (COPD) were previously reported in a region of 19q13, including CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response). The associated single nucleotide polymorphisms (SNPs) were assumed to be proxies for functional variation in CYP2A6. Here, we demonstrate that when CYP2A6 and EGLN2 genotypes are analyzed together, the key EGLN2 variant, rs3733829, is not associated with nicotine metabolism independent of CYP2A6, but is nevertheless independently associated with CPD, and with breath carbon monoxide (CO), a phenotype associated with cigarette consumption and relevant to hypoxia. SNPs in EGLN2 are also associated with nicotine dependence and with smoking efficiency (CO/CPD). These results indicate a previously unappreciated novel mechanism behind genome-wide significant associations with cigarette consumption and disease risk unrelated to nicotine metabolism.
- Subjects :
- Chromosomes, Human, Pair 19
Cytochrome P-450 CYP2A6
Genetic Variation
Genome-Wide Association Study
Genotype
Humans
Hypoxia genetics
Linkage Disequilibrium
Nicotine genetics
Polymorphism, Single Nucleotide
Risk Factors
Aryl Hydrocarbon Hydroxylases genetics
Carbon Monoxide analysis
Hypoxia-Inducible Factor-Proline Dioxygenases genetics
Nicotine metabolism
Smoking genetics
Tobacco Use Disorder genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2083
- Volume :
- 23
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Human molecular genetics
- Publication Type :
- Academic Journal
- Accession number :
- 24045616
- Full Text :
- https://doi.org/10.1093/hmg/ddt432