Variants in the 15q24/25 Locus Associate with Lung Function Decline in Active Smokers
| العنوان: | Variants in the 15q24/25 Locus Associate with Lung Function Decline in Active Smokers |
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| المؤلفون: | Jan-Willem J. Lammers, Pim A. de Jong, Els Wauters, Marc Decramer, Joanna Smolonska, H. Marike Boezen, Wim Janssens, Firdaus A. A. Mohamed Hoesein, Pieter Zanen, Harry J.M. Groen, Cisca Wijmenga, Diether Lambrechts, Dirkje S. Postma |
| المساهمون: | Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Research Institute for Asthma and COPD (GRIAC), Life Course Epidemiology (LCE), Vij, Neeraj |
| المصدر: | PLoS ONE, 8(1):e53219. PUBLIC LIBRARY SCIENCE PLoS ONE PLoS ONE, Vol 8, Iss 1, p e53219 (2013) PLoS ONE; Vol 8 |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Nicotinic Acetylcholine Receptors, Pathology, Anatomy and Physiology, Pulmonology, Chronic Obstructive Pulmonary Diseases, Epidemiology, medicine.medical_treatment, Respiratory System, Receptors, Nicotinic, Biochemistry, Gastroenterology, Pulmonary function testing, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, SUSCEPTIBILITY LOCUS, Lung, 0303 health sciences, COPD, education.field_of_study, Multidisciplinary, EPITHELIAL-CELLS, Forced Expiratory Flow Rates, Middle Aged, CANCER, 3. Good health, medicine.anatomical_structure, Genetic Epidemiology, Cohort, Medicine, Female, SMOKING, Research Article, Nicotine, medicine.medical_specialty, GENES, Substance-Related Disorders, Science, Population, OBSTRUCTIVE PULMONARY-DISEASE, 03 medical and health sciences, FEV1/FVC ratio, Internal medicine, Genetics, medicine, Humans, Lung transplantation, GENOME-WIDE ASSOCIATION, education, Biology, Aged, 030304 developmental biology, Chromosomes, Human, Pair 15, business.industry, Proteins, Smoking Related Disorders, Genetic Variation, 15Q25.1, medicine.disease, NICOTINE DEPENDENCE, Confidence interval, respiratory tract diseases, Protein Subunits, 030228 respiratory system, Genetic Loci, Genetics of Disease, SUBUNIT, business |
| الوصف: | Genetic variation in nicotinic acetylcholine receptor subunit genes (nAChRs) is associated with lung function level and chronic obstructive pulmonary disease (COPD). It is unknown whether these variants also predispose to an accelerated lung function decline. We investigated the association of nAChR susceptibility variants with lung function decline and COPD severity. The rs1051730 and rs8034191 variants were genotyped in a population-based cohort of 1,226 heavy smokers (COPACETIC) and in an independent cohort of 883 heavy smokers, of which 653 with COPD of varying severity (LEUVEN). Participants underwent pulmonary function tests at baseline. Lung function decline was assessed over a median follow-up of 3 years in COPACETIC. Current smokers homozygous for the rs1051730 A-allele or rs8034191 G-allele had significantly greater FEV(1)/FVC decline than homozygous carriers of wild-type alleles (3.3% and 4.3%, p = 0.026 and p = 0.009, respectively). In the LEUVEN cohort, rs1051730 AA-carriers and rs8034191 GG-carriers had a two-fold increased risk to suffer from COPD GOLD IV (OR 2.29, 95% confidence interval [CI] = 1.11-4.75; p = 0.025 and OR = 2.42, 95% [CI] = 1.18-4.95; p = 0.016, respectively). The same risk alleles conferred, respectively, a five- and four-fold increased risk to be referred for lung transplantation because of end-stage COPD (OR = 5.0, 95% [CI] = 1.68-14.89; p = 0.004 and OR = 4.06, 95% [CI] = 1.39-11.88; p = 0.010). In Europeans, variants in nAChRs associate with an accelerated lung function decline in current smokers and with clinically relevant COPD. ispartof: PLoS One vol:8 issue:1 ispartof: location:United States status: published |
| وصف الملف: | application/pdf; Print-Electronic |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee0383c42d194761cf4d278f41701f29Test https://doi.org/10.1371/journal.pone.0053219Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee0383c42d194761cf4d278f41701f29 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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