Genetic risk factors for chronic obstructive pulmonary disease

Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only a minority of cigarette smokers develop symptomatic disease. Studies of families and twins suggest that genetic factors also contribute to the development of COPD. We present a detailed literature review of the genes which have been investigated as potential risk factors for this disease. The only established genetic risk factor for COPD is homozygosity for the Z allele of the alpha1-antitrypsin gene. Heterozygotes for the Z allele may also be at increased risk. Other mutations affecting the structure of alpha1-antitrypsin or the regulation of gene expression have been identified as risk factors. Genes, including those for alpha1-antichymotrypsin, alpha2-macroglobulin, vitamin D-binding protein and blood group antigens, have also been associated with the development of COPD. Variants of the cystic fibrosis transmembrane regulator gene have been identified as risk factors for disseminated bronchiectasis. The genetic basis to chronic obstructive pulmonary disease has begun to be elucidated and it is likely that several genes will be implicated in the pathogenesis of this disease. The knowledge gained from such studies may also prove relevant to other inflammatory diseases.

This article has been cited by other articles:

				E. Cavarra, P. Fardin, S. Fineschi, A. Ricciardi, G. De Cunto, F. Sallustio, M. Zorzetto, M. Luisetti, U. Pfeffer, G. Lungarella, et al. Early response of gene clusters is associated with mouse lung resistance or sensitivity to cigarette smoke Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L418 - L429. [Abstract] [Full Text] [PDF]

				R P Young, R Hopkins, P N Black, C Eddy, L Wu, G D Gamble, G D Mills, J E Garrett, T E Eaton, and M I Rees Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function Thorax, May 1, 2006; 61(5): 394 - 399. [Abstract] [Full Text] [PDF]

				B. Hapcioglu, H. Issever, E. Kocyigit, R. Disci, S. Vatansever, and K. Ozdilli The Effect of Air Pollution and Meteorological Parameters on Chronic Obstructive Pulmonary Disease at an Istanbul Hospital Indoor and Built Environment, April 1, 2006; 15(2): 147 - 153. [Abstract] [PDF]

				K. R. Chapman, D. M. Mannino, J. B. Soriano, P. A. Vermeire, A. S. Buist, M. J. Thun, C. Connell, A. Jemal, T. A. Lee, M. Miravitlles, et al. Epidemiology and costs of chronic obstructive pulmonary disease Eur. Respir. J., January 1, 2006; 27(1): 188 - 207. [Full Text] [PDF]

				T. L. Petty Are COPD and Lung Cancer Two Manifestations of the Same Disease? Chest, October 1, 2005; 128(4): 1895 - 1897. [Full Text] [PDF]

				F. Rodriguez, C. de la Roza, R. Jardi, M. Schaper, R. Vidal, and M. Miravitlles Glutathione S-Transferase P1 and Lung Function in Patients With {alpha}1-Antitrypsin Deficiency and COPD Chest, May 1, 2005; 127(5): 1537 - 1543. [Abstract] [Full Text] [PDF]

				A. Lindberg, A.-C. Jonsson, E. Ronmark, R. Lundgren, L.-G. Larsson, and B. Lundback Ten-Year Cumulative Incidence of COPD and Risk Factors for Incident Disease in a Symptomatic Cohort Chest, May 1, 2005; 127(5): 1544 - 1552. [Abstract] [Full Text] [PDF]

				C. Reinhard, B. Meyer, H. Fuchs, T. Stoeger, G. Eder, F. Ruschendorf, J. Heyder, P. Nurnberg, M. H. de Angelis, and H. Schulz Genomewide Linkage Analysis Identifies Novel Genetic Loci for Lung Function in Mice Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 880 - 888. [Abstract] [Full Text] [PDF]

				B. Bartalesi, E. Cavarra, S. Fineschi, M. Lucattelli, B. Lunghi, P. A. Martorana, and G. Lungarella Different lung responses to cigarette smoke in two strains of mice sensitive to oxidants Eur. Respir. J., January 1, 2005; 25(1): 15 - 22. [Abstract] [Full Text] [PDF]

				C P Hersh, M Dahl, N P Ly, C S Berkey, B G Nordestgaard, and E K Silverman Chronic obstructive pulmonary disease in {alpha}1-antitrypsin PI MZ heterozygotes: a meta-analysis Thorax, October 1, 2004; 59(10): 843 - 849. [Abstract] [Full Text] [PDF]

				R A Sandhaus {alpha}1-Antitrypsin deficiency {middle dot} 6: New and emerging treatments for {alpha}1-antitrypsin deficiency Thorax, October 1, 2004; 59(10): 904 - 909. [Abstract] [Full Text] [PDF]

				V. A. De Palo Pulmonary Disease: Pneumonia, Chronic Obstructive Pulmonary Disease, Asthma, and Thromboembolic Disease J Am Podiatr Med Assoc, March 1, 2004; 94(2): 157 - 167. [Abstract] [Full Text] [PDF]

				I Kasuga, P D Pare, J Ruan, J E Connett, N R Anthonisen, and A J Sandford Lack of association of group specific component haplotypes with lung function in smokers Thorax, September 1, 2003; 58(9): 790 - 793. [Abstract] [Full Text] [PDF]

				S.T. Weiss, D.L. DeMeo, and D.S. Postma COPD: problems in diagnosis and measurement Eur. Respir. J., June 1, 2003; 21(41_suppl): 4S - 12s. [Abstract] [Full Text] [PDF]

				J. B. Wilk, A. L. DeStefano, D. K. Arnett, S. S. Rich, L. Djousse, R. O. Crapo, M. F. Leppert, M. A. Province, L. A. Cupples, D. J. Gottlieb, et al. A Genome-Wide Scan of Pulmonary Function Measures in the National Heart, Lung, and Blood Institute Family Heart Study Am. J. Respir. Crit. Care Med., June 1, 2003; 167(11): 1528 - 1533. [Abstract] [Full Text] [PDF]

				L. J. Palmer, J. C. Celedon, H. A. Chapman, F. E. Speizer, S. T. Weiss, and E. K. Silverman Genome-wide linkage analysis of bronchodilator responsiveness and post-bronchodilator spirometric phenotypes in chronic obstructive pulmonary disease Hum. Mol. Genet., May 15, 2003; 12(10): 1199 - 1210. [Abstract] [Full Text] [PDF]

				I. Ferrarotti, M. Zorzetto, M. Beccaria, L.S. Gile, R. Porta, N. Ambrosino, P.F. Pignatti, I. Cerveri, E. Pozzi, and M. Luisetti Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema Eur. Respir. J., March 1, 2003; 21(3): 444 - 449. [Abstract] [Full Text] [PDF]

				A J Sandford and E K Silverman Chronic obstructive pulmonary disease * 1: Susceptibility factors for COPD the genotype-environment interaction Thorax, August 1, 2002; 57(8): 736 - 741. [Abstract] [Full Text] [PDF]

				T. L. Petty COPD in Perspective* Chest, May 1, 2002; 121 (2009): 116S - 120S. [Abstract] [Full Text] [PDF]

				O. JOOST, J. B. WILK, L. ADRIENNE CUPPLES, M. HARMON, A. M. SHEARMAN, C. T. BALDWIN, G. T. O'CONNOR, R. H. MYERS, and D. J. GOTTLIEB Genetic Loci Influencing Lung Function . A Genomewide Scan in the Framingham Study Am. J. Respir. Crit. Care Med., March 15, 2002; 165(6): 795 - 799. [Abstract] [Full Text] [PDF]

				J.R. Hoidal Genetics of COPD: present and future Eur. Respir. J., November 1, 2001; 18(5): 741 - 743. [Full Text] [PDF]

				T. Ishii, N. Keicho, S. Teramoto, A. Azuma, S. Kudoh, Y. Fukuchi, Y. Ouchi, and T. Matsuse Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis Eur. Respir. J., November 1, 2001; 18(5): 753 - 757. [Abstract] [Full Text] [PDF]

				E. CAVARRA, B. BARTALESI, M. LUCATTELLI, S. FINESCHI, B. LUNGHI, F. GAMBELLI, L. A. ORTIZ, P. A. MARTORANA, and G. LUNGARELLA Effects of Cigarette Smoke in Mice with Different Levels of alpha 1-Proteinase Inhibitor and Sensitivity to Oxidants Am. J. Respir. Crit. Care Med., September 1, 2001; 164(5): 886 - 890. [Abstract] [Full Text] [PDF]

				J.M. Anto, P. Vermeire, J. Vestbo, and J. Sunyer Epidemiology of chronic obstructive pulmonary disease Eur. Respir. J., May 1, 2001; 17(5): 982 - 994. [Abstract] [Full Text] [PDF]

				L.J. Palmer, M.W. Knuiman, M.L. Divitini, P.R. Burton, A.L. James, H.C. Bartholomew, G. Ryan, and A.W. Musk Familial aggregation and heritability of adult lung function: results from the Busselton Health Study Eur. Respir. J., April 1, 2001; 17(4): 696 - 702. [Abstract] [Full Text] [PDF]

				P Suadicani, H O Hein, H W Meyer, and F Gyntelberg Exposure to cold and draught, alcohol consumption, and the NS-phenotype are associated with chronic bronchitis: an epidemiological investigation of 3387 men aged 53-75 years: the Copenhagen Male Study Occup. Environ. Med., March 1, 2001; 58(3): 160 - 164. [Abstract] [Full Text]

				S. Teramoto, T. Ishii, M. Luisetti, and P. F. Pignatti No Association of Tumor Necrosis Factor-{{alpha}} Gene Polymorphism and COPD in Caucasian Smokers and Japanese Smokers Chest, January 1, 2001; 119(1): 315 - 316. [Full Text] [PDF]

				N. Fujitani, Y. Liu, T. Okamura, and H. Kimura Distribution of H Type 1-4 Chains of the ABO(H) System in Different Cell Types of Human Respiratory Epithelium J. Histochem. Cytochem., December 1, 2000; 48(12): 1649 - 1656. [Abstract] [Full Text]

				P. J. Barnes Chronic Obstructive Pulmonary Disease N. Engl. J. Med., July 27, 2000; 343(4): 269 - 280. [Full Text] [PDF]

				C. Patuzzo, L. S. Gile, M. Zorzetto, E. Trabetti, G. Malerba, P. F. Pignatti, and M. Luisetti Tumor Necrosis Factor Gene Complex in COPD and Disseminated Bronchiectasis Chest, May 1, 2000; 117(5): 1353 - 1358. [Abstract] [Full Text] [PDF]

				W. MacNee Oxidants/Antioxidants and COPD Chest, May 1, 2000; 117 (2009): 303S - 317S. [Abstract] [Full Text] [PDF]

				W. MACNEE and I. RAHMAN Oxidants and Antioxidants as Therapeutic Targets in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S58 - 65. [Abstract] [Full Text] [PDF]

				N. M. Siafakas, E. G. Tzortzaki, G. Sourvinos, D. Bouros, N. Tzanakis, A. Kafatos, and D. Spandidos Microsatellite DNA Instability in COPD Chest, July 1, 1999; 116(1): 47 - 51. [Abstract] [Full Text] [PDF]

				A. J. SANDFORD, T. CHAGANI, J. J. SPINELLI, and P. D. PARE alpha 1-Antitrypsin Genotypes and the Acute-phase Response to Open Heart Surgery Am. J. Respir. Crit. Care Med., May 1, 1999; 159(5): 1624 - 1628. [Abstract] [Full Text] [PDF]

				P. J Barnes Genetics and pulmonary medicine bullet  9: Molecular genetics of chronic obstructive pulmonary disease Thorax, March 1, 1999; 54(3): 245 - 252. [Full Text]

				L. Fabbri, B. Beghé, G. Caramori, A. Papi, and M. Saetta Similarities and discrepancies between exacerbations of asthma and chronic obstructive pulmonary disease Thorax, September 1, 1998; 53(9): 803 - 808. [Full Text]

				R. M. SENIOR and N. R. ANTHONISEN Chronic Obstructive Pulmonary Disease (COPD) Am. J. Respir. Crit. Care Med., April 1, 1998; 157(4): S139 - S147. [Full Text] [PDF]

				D. SCHELLENBERG, P. D. PARE, T. D. WEIR, J. J. SPINELLI, B. A. M. WALKER, and A. J. SANDFORD Vitamin D Binding Protein Variants and the Risk of COPD Am. J. Respir. Crit. Care Med., March 1, 1998; 157(3): 957 - 961. [Abstract] [Full Text] [PDF]