Genetic Implications in COPD. The Current Knowledge

DOI: 10.4236/ojrd.2013.32009   PDF   HTML     4,831 Downloads   10,998 Views   Citations


Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial disease in the pathogenesis of which contributes a variety of causative factors including genetic and environmental ones. They may also be interactions of genetic susceptibilities and environmental influences. Towards to that in the pathogenesis of the disease except smoking, it seems to have a great impact the genetic predisposition of the individuals suffering from that serious progressive disease. Regarding to these observations and findings very interesting studies have been conducted in order to elucidate the implications of different genes, and their polymorphisms in disease aetiology. This is a review which elucidates the impact of genetic susceptibility in COPD.

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Sotiriou, I. and Makris, D. (2013) Genetic Implications in COPD. The Current Knowledge. Open Journal of Respiratory Diseases, 3, 52-62. doi: 10.4236/ojrd.2013.32009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] “Definition and Mechanisms Underlying Airflow Limitation in COPD, Risk Factors in COPD,” In: Global Initiative for COPD, GOLD Guidelines, 2006.
[2] B. Burrows, R. J. Knudson, M. G. Cline and M. D. Lebowitz, “Quantitative Relationships between Cigarette Smoking and Ventilatory Function,” American Review Respiratory Disease, Vol. 115, No. 2, 1977, pp. 195-205.
[3] C. Fletcher, R. Peto, C. Tinker and F. E. Speizer, “Factors Related to the Development of Airflow Obstruction,” In: The Natural History of Chronic Bronchitis and Emphysema, Oxford University Press, Oxford, 1976, pp. 70-105.
[4] S. Redline, P. V. Tishler, B. Rosner, F. I. Lewitter, M. Vandenburgh, S. T. Weis and F. E. Speizer, “Genotypic and Phenotypic Similarities in Pulmonary Function among Family Members of Adult Monozygotic and Dizygotic Twins,” American Journal of Epidemiology, Vol. 129, No. 4, 1989, pp. 827-836.
[5] F. I. Lewitter, I. B. Tager, M. McGue, P. V. Tishler and F. E. Speizer, “Genetic and Environmental Determinants of Level of Pulmonary Function,” American Journal of Epidemiology, Vol. 120, No. 4, 1984, pp. 518-529.
[6] F. Kueppers, R. D. Miller, H. Gordon, N. G. Hepper and K. Offord, “Familial Prevalence of Chronic Obstructive Pulmonary Disease in a Matched Pair Study,” American Journal of Medicine, Vol. 63, No. 3, 1977, pp. 336-342. doi:10.1016/0002-9343(77)90270-4
[7] B. H. Cohen, et al., “Chronic Obstructive Pulmonary Disease: A Challenge in Genetic Epidemiology,” American Journal of Epidemiology, Vol. 112, No. 2, 1980, pp. 274-288.
[8] N. R. Hackett, et al., “Variability of Antioxidant-Related Gene Expression in the Airway Epithelium of Cigarette Smokers,” American Journal of Respiratory Cell and Molecular Biology, Vol. 29, No. 3, 2003, pp. 331-343. doi:10.1165/rcmb.2002-0321OC
[9] P. Turnpenny and S. Ellard, “Emery’s Elements of Medical Genetics,” 12th Edition, Elsevier Churchill Livingstone, Edinburg, 2005.
[10] M. A. Varela and W. Amos, “Heterogeneous Distribution of SNPs in the Human Genome: Microsatellites as Predictors of Nucleotide Diversity and Divergence,” Genomics, Vol. 95, No. 3, 2010, pp. 151-159. doi:10.1016/j.ygeno.2009.12.003
[11] D. Makris, et al., “Microsatellite DNA Instability and COPD Exacerbations,” European Respiratory Journal, Vol. 32, No. 3, 2008, pp. 612-618. doi:10.1183/09031936.00169307
[12] N. M. Siafakas, et al., “Microsatellite DNA Instability in COPD,” Chest, Vol. 116, No. 1, 1999, pp. 47-51. doi:10.1378/chest.116.1.47
[13] A. J. Sandford, T. Chaqani, T. D. Weir, J. E. Connet, N. R. Anthonisen and P. D. Pare, “Susceptibility Genes for Rapid Decline of Lung Function in the Lung Health Study,” American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 2, 2001, pp. 469-473. doi:10.1164/ajrccm.163.2.2006158
[14] O. Joost, et al., “Genetic Loci Influencing Lung Function: A Genome-Wide Scan in Framingham Study,” American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 6, 2002, pp. 795-799. doi:10.1164/ajrccm.165.6.2102057
[15] J. Q. He, J. Ruan, J. E. Connett, N. R. Anthonisen, P. D. Pare and A. J. Sandford, “Antioxidant Gene Polymorphisms and Susceptibility to a Rapid Decline in Lung Function in Smokers,” American Journal of Respiratory and Critical Care Medicine, Vol. 166, No. 3, 2002, pp. 323-328. doi:10.1164/rccm.2111059
[16] J. Brogger, V. M. Steen, H. J. Eiken, A. Gulsvik and P. Bakke, “Genetic Association between COPD and Polymorphisms in TNF, ADRB2 and EPHX1,” European Respiratory Journal, Vol. 27, No. 4, 2006, pp. 682-688. doi:10.1183/09031936.06.00057005
[17] G. Hu, Z. Shi, J. Hu, G. Zou, G. Peng and P. Ran, “Association between Polymorphisms of Microsomal Epoxide Hydrolase and COPD: Results from Meta-Analyses,” Respirology, Vol. 13, No. 6, 2008, pp. 837-850. doi:10.1111/j.1440-1843.2008.01356.x
[18] R. Lakhdar, et al., “Microsomal Epoxide Hydrolase Gene Polymorphisms and Susceptibility to Chronic Obstructive Pulmonary Disease in the Tunisian Population,” Genetic Testing and Molecular Biomarkers, Vol. 14, No. 6, 2010, pp. 857-863. doi:10.1089/gtmb.2009.0168
[19] A. E. Hegab, et al., “Polymorphisms of IL4, IL13, and ADRB2 Genes in COPD,” Chest, Vol. 126, No. 6, 2004, pp. 1832-1839. doi:10.1378/chest.126.6.1832
[20] T. C. Van der Pouw Kraan, et al., “Chronic Obstructive Pulmonary Disease Is Associated with the -1055 IL-13 Promoter Polymorphism,” Genes and Immunity, Vol. 3, No. 7, 2002, pp. 436-439. doi:10.1038/sj.gene.6363896
[21] S. F. Liu, et al., “Il13 Promoter (-1055) Polymorphisms Associated with Chronic Obstructive Pulmonary Disease in Taiwanese,” Experimental Lung Research, Vol. 35, No. 10, 2009, pp. 807-816. doi:10.3109/01902140902893644
[22] L. I. Ho, et al., “Polymorphism of the Beta(2)-Adrenoceptor in COPD in Chinese Subjects,” Chest, Vol. 120, No. 5, 2001, pp. 1493-1499. doi:10.1378/chest.120.5.1493
[23] K. Hirano, et al., “Tissue Inhibitor of Metalloproteinases-2 Gene Polymorphisms in Chronic Obstructive Pulmonary Disease,” European Respiratory Journal, Vol. 18, No. 5, 2001, pp. 748-752. doi:10.1183/09031936.01.00102101
[24] L. Joos, et al., “The Role of Matrix Metalloproteinase Polymorphisms in the Rate of Decline in Lung Function,” Human Molecular Genetics, Vol. 11, No. 5, 2002, pp. 569-576. doi:10.1093/hmg/11.5.569
[25] A. G. Wilson, F. S. di Giovine, A. I. Blakemore and G. W. Duff, “Single Base Polymorphism in the Tumour Necrosis Factor Alpha Gene Is Detectable by NcoI Restriction of PCR Product,” Human Molecular Genetics, Vol. 1, No. 5, 1992, p. 353. doi:10.1093/hmg/1.5.353
[26] N. Chieracul, P. Wongwisutikul, S. Vejbaesya and K. Chotvilaiwan, “Tumor Necrosis Factor-Alpha Gene Promoter Polymorphism Is Not Associated with Smoking-Related COPD in Thailand,” Respirology, Vol. 10, No. 1, 2005, pp. 36-39. doi:10.1111/j.1440-1843.2005.00626.x
[27] G. P. Hu, G. Y. Peng, J. X. Hu and P. X. Pan, “Association of Tumor Necrosis Factor Alpha 308 G/A Gene Promoter Polymorphism with the Presence of Chronic Obstructive Pulmonary Disease: A Meta-Analysis,” Chinese Journal of Tuberculosis and Respiratory Diseases, Vol. 30, No. 8, 2007, pp. 588-594.
[28] P. Zhan, et al., “TNF-308 Gene Polymorphism Is Associated with COPD Risk among Asians: Meta-Analysis of Data for 6118 Subjects,” Molecular Biology Reports, Vol. 38, No. 1, 2011, pp. 219-227. doi:10.1007/s11033-010-0098-y
[29] L. Wu, J. Chau, et al., “Transforming Growth Factor-β1 Genotype and Susceptibility to Chronic Obstructive Pulmonary Disease,” Thorax, Vol. 59, No. 2, 2004, pp. 126-129. doi:10.1136/thorax.2003.005769
[30] C. C. Van Diemen, D. S. Postma, J. M. Vonk, M. Bruinenberg, I. M. Nolte and H. M. Boezen, “Decorin and TGF-Beta1 Polymorphisms and Development of COPD in a General Population,” Respiratory Research, Vol. 16, No. 7, 2006, p. 89. doi:10.1186/1465-9921-7-89
[31] H. I. Yoon, et al., “Lack of Association between COPD and Transforming Growth Factor-Beta1 (TGFB1) Genetic Polymorphisms in Koreans,” International Journal of Tuberculosis and Lung Disease, Vol. 10, No. 5, 2006, pp. 504-509.
[32] M. Bodas, T. Min, S. Mazur and N. Vij, “Critical Modifier Role of Membrane-Cystic Fibrosis Transmembrane Conductance Regulator-Dependent Ceramide Signaling in Lung Injury and Emphysema,” Journal of Immunology, Vol. 186, No. 1, 2011, pp. 602-613. doi:10.4049/jimmunol.1002850
[33] N. Minematsu, H. Nakamura, et al., “Association of CYP2A6 Deletion Polymorphisms with Smoking Habit and Development of Pulmonary Emphysema,” Thorax, Vol. 58, No. 7, 2003, pp. 623-628. doi:10.1136/thorax.58.7.623
[34] N. Yamamoto, S. Homma, et al., “Vitamin D3 Binding Protein (Groupspecific Component) Is a Precursor for the Macrophage-Activating Signal Factor from Lysophosphatidylcholine-Treated Lymphocytes,” Proceedings of the National Academy Science USA, Vol. 88, No. 19, 1991, pp. 8539-8543. doi:10.1073/pnas.88.19.8539
[35] R. R. Kew, R. O. Webster, et al., “Gc-Globulin (Vitamin D-Binding Protein) Enhances the Neutrophil Chemotactic activity of C5a and C5a des Arg,” Journal of Clinical Investigation, Vol. 82, No. 1, 1998, pp. 364-369. doi:10.1172/JCI113596
[36] S. J. Di Martino, A. B. Shah, G. Trujillo and R. R. Kew, “Elastase Controls the Binding of the Vitamin D-Binding Protein (Gc-Globulin) to Neutrophils: A Potential Role in the Regulation of C5a Co-Chemotactic Activity,” The Journal of Immunology, Vol. 166, No. 4, 2001, pp. 2688-2694.
[37] I. Ito, et al., “Risk and Severity of COPD Is Associated with the Group-Specific Component of Serum Globulin 1F Allele,” Chest Journal, Vol. 125, No. 1, 2004, pp. 63-70. doi:10.1378/chest.125.1.63
[38] M. Lu, B. Yang and Y. Y. Cai, “The Relationship between Vitamin D Binding Protein Gene Polymorphism and Chronic Obstructive Pulmonary Disease,” Chinese Journal of Internal Medicine, Vol. 43, No. 2, 2004, pp. 117-120.
[39] L. H. Shen, et al., “Association of Vitamin D Binding Protein Variants with Susceptibility to Chronic Obstructive Pulmonary Disease,” Journal of International Medical Research, Vol. 38, No. 3, 2010, pp. 1093-1098.
[40] M. Kuro-o, Y. Matsumura, et al., “Mutation of the Mouse Klotho Gene Leads to a Syndrome Resembling Aging,” Nature, Vol. 390, No. 6655, 1997, pp. 45-51. doi:10.1038/36285
[41] N. A. Molfino, “Genetics of COPD,” Chest Journal, Vol. 125, No. 5, 2004, pp. 1929-1940. doi:10.1378/chest.125.5.1929
[42] Y. Saito, T. Nakamura, Y. Ohyama, et al., “In Vivo Klotho Gene Delivery Protects Against Endothelial Dysfunction in Multiple Risk Factor Syndrome,” Biochemical and Biophysical Research Communications, Vol. 276, No. 2, 2000, pp. 767-772. doi:10.1006/bbrc.2000.3470
[43] D. E. Arking, et al., “Klotho Allele Status and the Risk of Early-Onset Occult Coronary Artery Disease” The American Journal of Human Genetics, Vol. 72, No. 5, 2003, pp. 1154-1161. doi:10.1086/375035
[44] K. Kawano, N. Ogata, et al., “Klotho Gene Polymorphisms Associated with Bone Density of Aged Postmenopausal Women,” Journal of Bone and Mineral Research, Vol. 17, No. 10, 2002, pp. 1744-1751. doi:10.1359/jbmr.2002.17.10.1744
[45] I. Sotiriou, M. Froudarakis, et al., “Klotho Gene Polymorphism -395G>A in Patients with Chronic Obstructive Pulmonary Disease (COPD),” Pneumon, Vol. 23, No. 4, 2010, pp. 342-347.
[46] N. Hizawa, et al., “β2-Adrenergic Receptor Genetic Polymorphisms and Short-Term Bronchodilator Responses in Patients with COPD,” Chest Journal, Vol. 132, No. 5, 2007, pp. 1485-1492. doi:10.1378/chest.07-1103
[47] M. Mokry, P. Joppa, et al., “β2-Adrenergic Receptor Haplotype and Bronchodilator Response to Salbutamol in Patients with Acute Exacerbations of COPD,” Medical Science Monitor, Vol. 14, No. 8, 2008, pp. 392-398.
[48] W. J. Kim, Y. M. Oh, et al., “Lung Function Response to 12-Week Treatment with Combined Inhalation of Long-Acting β2 Agonist and Glucocorticoid According to ADRB2 Polymorphism in Patients with Chronic Obstructive Pulmonary Disease,” Lung, Vol. 186, No. 6, 2008, pp. 381-386. doi:10.1007/s00408-008-9103-9
[49] N. Umeda, T. Yoshikawa, H. Kanazawa, K. Hirata and S. Fujimoto, “Association of β2-Adrenoreceptor Genotypes with Bronchodilatory Effect of Tiotropium in COPD,” Respirology, Vol. 13, No. 3, 2008, pp. 346-352. doi:10.1111/j.1440-1843.2008.01259.x
[50] N. M. Siafakas and E. G. Tzortzaki, “Few Smokers Develop COPD. Why?” Respiratory Medicine, Vol. 96, No. 8, 2002, pp. 615-624. doi:10.1053/rmed.2002.1318
[51] T. Nagai, K. Yamada, et al., “Cognition Impairment in the Genetic Model of Aging Klotho Gene Mutant Mice: A Role of Oxidative Stress,” The FASEB Journal, Vol. 17, No. 1, 2003, pp. 50-52.
[52] E. G. Tzortzaki and N. M. Siafakas, “A Hypothesis for Initiation of COPD,” European Respiratory Journal, Vol. 34, No. 2, 2009, pp. 310-315. doi:10.1183/09031936.00067008

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