Chronic Obstructive Pulmonary Disease (COPD) is a complex disease with varying susceptibility. COPD development may be associated with copy number variation (CNV) in susceptible genomic regions. CNV also contributes to COPD heritability as these can cause changes in DNA fragment. CNVs in COPD smokers and COPD ex-smokers have not been examined so far. Thus, genome-wide array based comparative genomic hybridization (aCGH) was performed in COPD (n = 15) and control subjects (n = 13) to identify the vulnerable candidate genes for genetic susceptibility and CNVs in smoker (n = 6) and ex-smoker (n = 9) COPD and compare it with control subjects to identify the candidate genes potentially involved in the pathogenesis of COPD. Copy number gains and losses were detected in several chromosomal regions.
Chromosomal regions found to be consistently associated with both subgroups of COPD, as well as, of control group were: 2p11.2, 4q13.2, 8p23.1, 8p11.22, 12p13.31 and 14q32.33. Chromosomal regions associated with COPD were 11p15.5, 15q11.1-q11.2 and Xq28, which had several genes, (viz., CHECK2P2, HERC2P3, GOLGA6L6 and GOLGA8CP) which were associated with COPD smokers, while several other genes (viz., LICAM, LCA10, AVPR2, GDI1, HOTS and H19) were found to be associated with COPD ex-smokers. These loci and genes may be explored further for their potential use as predictive markers and better understanding of pathophysiology of COPD.
Raherison C, Girodet P-O. ''Epidemiology of COPD,'' Eur Respir Rev, vol. 18, pp. 213–21, Dec 2009.
Soriano JB, Agusti A. ''The graphic of COPD: or balancing repair (yang) and inflammation (yin),'' Eur Respir J, vol. 32, pp. 1426-7, Dec 2008.
Spurzem MJR, Rennard MSI, Spurzem MJR, Rennard MSI, Jay. ''Pathogenesis of COPD,'' Semin Respir Crit Care Med, vol. 26, pp. 142-53, Apr 2006.
Laniado-Laborín R. ''Smoking and Chronic Obstructive Pulmonary Disease (COPD). Parallel Epidemics of the 21st Century,'' Int J Environ Res Public Health, vol. 6, pp. 209-24, Jan 2009.
Zeng G, Sun B, Zhong N. ''Non-smoking-related chronic obstructive pulmonary disease: a neglected entity?,'' Respirol Carlton Vic, vol. 17, pp. 908-12, Aug 2012.
Larson RK, Barman ML, Kueppers F. ''Genetic and Environmental Determinants of Chronic Obstructive Pulmonary Disease,'' Ann Intern Med, vol. 72, pp. 627-32, May 1970.
Tager IB, Rosner B, Tishler PV, Speizer FE, Kass EH. ''Household aggregation of pulmonary function and chronic bronchitis,'' Am Rev Respir Dis, vol. 114, pp. 485-92, Sep 1976.
Seifart C, Plagens A. ''Genetics of chronic obstructive pulmonary disease,'' Int J Chron Obstruct Pulmon Dis, vol. 2, pp. 541-550, Dec 2007.
Li LSK, Paquet C, Johnston K, Williams MT. “What are my chances of developing COPD if one of my parents has the disease?” A systematic review and meta-analysis of prevalence of co-occurrence of COPD diagnosis in parents and offspring,'' Int J Chron Obstruct Pulmon Dis, vol. 12, pp. 403-15, Jan 2017.
Stolk J, Seersholm N, Kalsheker N. ''Alpha1-antitrypsin deficiency: current perspective on research, diagnosis, and management,'' Int J Chron Obstruct Pulmon Dis, vol. 1, pp-151-60, Jun 2006.
Bashir A, Shah NN, Hazari YM, Habib M, Bashir S, Hilal N, et al. ''Novel variants of SERPIN1A gene: Interplay between alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease,'' Respir Med, vol. 117, pp. 139-49, Aug 2016.
Givelber RJ, Couropmitree NN, Gottlieb DJ, Evans JC, Levy D, Myers RH, et al. ''Segregation Analysis of Pulmonary Function among Families in the Framingham Study,'' Am J Respir Crit Care Med, vol. 157, pp. 1445-51, May 1998.
Ionita-Laza I, Rogers AJ, Lange C, Raby BA, Lee C. ''Genetic association analysis of copy number variation (CNVs) in human disease pathogenesis,'' Genomics, vol. 93, pp. 22-6, Jan 2009.
Scherer SW, Lee C, Birney E, Altshuler DM, Eichler EE, Carter NP, et al. ''Challenges and standards in integrating surveys of structural variation,'' Nat Genet, vol. 39, pp. S7-15, Jul 2007.
Hovhannisyan G, Harutyunyan T, Aroutiounian R, Liehr T. ''DNA Copy Number Variations as Markers of Mutagenic Impact,'' Int J Mol Sci, vol. 20, pp. 4723, Oct 2019.
Choy KW, Setlur SR, Lee C, Lau TK. ''The impact of human copy number variation on a new era of genetic testing,'' BJOG Int J Obstet Gynaecol, vol. 117, pp. 391-8, Feb 2010.
Freeman JL. ''Copy number variation: New insights in genome diversity,'' Genome Res, vol. 16, pp. 949-61, Jun 2006.
Tuzun E, Sharp AJ, Bailey JA, Kaul R, Morrison VA, Pertz LM, et al. ''Fine-scale structural variation of the human genome,'' Nat Genet, vol. 37, pp. 727-32, Jul 2005.
Russo CD, Di Giacomo G, Cignini P, Padula F, Mangiafico L, Mesoraca A, et al. ''Comparative study of aCGH and Next Generation Sequencing (NGS) for chromosomal microdeletion and microduplication screening,'' J Prenat Med, vol. 8, pp. 57-69, Apr 2014.
Lucito R, Healy J, Alexander J, Reiner A, Esposito D, Chi M, et al. ''Representational Oligonucleotide Microarray Analysis: A High-Resolution Method to Detect Genome Copy Number Variation,'' Genome Res, vol. 13, pp. 2291-305, Oct 2003.
Dawson AJ, Yanofsky R, Vallente R, Bal S, Schroedter I, Liang L, et al. ''Array comparative genomic hybridization and cytogenetic analysis in pediatric acute leukemias,'' Curr Oncol, vol. 18, pp. e210, Oct 2011.
Gullotta F, Biancolella M, Costa E, Colapietro I, Nardone AM, Molinaro P, et al. ''Prenatal diagnosis of genomic disorders and chromosome abnormalities using array-based comparative genomic hybridization,'' J Prenat Med, vol. 1, pp. 16-22, Jan 2007.
Gao J, Liu C, Yao F, Hao N, Zhou J, Zhou Q, et al. ''Array-based comparative genomic hybridization is more informative than conventional karyotyping and fluorescence in situ hybridization in the analysis of first-trimester spontaneous abortion,'' Mol Cytogenet, vol. 5, pp. 33, Jul 2012.
Coughlin CR, Scharer GH, Shaikh TH. ''Clinical impact of copy number variation analysis using high-resolution microarray technologies: advantages, limitations and concerns,'' Genome Med, vol. 4, pp. 1-12, Oct 2012.
Nowakowska B. ''Clinical interpretation of copy number variants in the human genome,'' J Appl Genet, vol. 58, pp. 449-57, Nov 2017.
Choi JS, Lee WJ, Baik SH, Yoon HK, Lee K-H, Kim YH, et al. ''Array CGH Reveals Genomic Aberrations in Human Emphysema,'' Lung, vol. 187, pp. 165-72, Jun 2009.
Boelens MC, Gustafson AM, Postma DS, Kok K, van der Vries G, van der Vlies P, et al. ''A chronic obstructive pulmonary disease related signature in squamous cell lung cancer,'' Lung Cancer, vol. 72, pp. 177-83, May 2011.
Hua L, Yang Z, Zhou P, An L. ''Using Comparative Genomic Hybridization Arrays (aCGH) Techniques to Detect Chronic Obstructive Pulmonary Disease Related Susceptibility Regions,'' International Journal of Bio-Science and Bio-Technology, vol. 5, pp. 121-130, Jan 2013.
Hobbs BD, de Jong K, Lamontagne M, Bossé Y, Shrine N, Artigas MS, et al. ''Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis,'' Nat Genet, vol. 49, pp. 426-32, Mar 2017.
Wain LV, Shrine N, Artigas MS, Erzurumluoglu AM, Noyvert B, Bossini-Castillo L, et al. ''Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets,'' Nat Genet, vol. 49, pp. 416-25, Mar 2017.
Aljohani HM, Aittaleb M, Furgason JM, Amaya P, Deeb A, Chalmers JJ, et al. ''Genetic mutations associated with lung cancer metastasis to the brain,'' Mutagenesis, vol. 33, pp. 137-45, Apr 2018.
Gao W, Zhang C, Ma T, Wen S, Fu R, Zhao D, et al. ''Potential biomarkers and their regulatory relationships in laryngeal squamous cell carcinoma with lymph node metastasis revealed by integrating mRNA, microRNA and long non-coding RNA profiles,'' Int J Clin Exp Pathol, vol, 9, pp. 5103-16, May 2016.
Eichler EE. ''Masquerading repeats: paralogous pitfalls of the human genome,'' Genome Res, vol. 8, pp. 758-62, Aug 1998.
Pujana MA, Nadal M, Gratacòs M, Peral B, Csiszar K, González-Sarmiento R, et al. ''Additional Complexity on Human Chromosome 15q: Identification of a Set of Newly Recognized Duplicons (LCR15) on 15q11–q13, 15q24, and 15q26,'' Genome Res, vol.11, pp. 98-111, Jan 2001.
Chen J, Cai H, Xie Y, Jiang H. ''Targeting long non-coding RNA HERC2P3 inhibits cell growth and migration in human gastric cancer cells,'' International Journal of Clinical and Experimental Pathology, vol. 10, pp. 7632-9, Jul 2017.
Liu JZ, Tozzi F, Waterworth DM, Pillai SG, Muglia P, Middleton L, et al. ''Meta-analysis and imputation refines the association of 15q25 with smoking quantity,'' Nat Genet, vol. 42, pp. 436-40, May 2010.
Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, et al. ''A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25,'' Nature, vol. 452, pp. 633-7, Apr 2008.
Nedeljkovic I, Terzikhan N, Vonk JM, van der Plaat DA, Lahousse L, van Diemen CC, et al. ''A Genome-Wide Linkage Study for Chronic Obstructive Pulmonary Disease in a Dutch Genetic Isolate Identifies Novel Rare Candidate Variants,'' Front Genet, vol. 9, pp. 133, Apr 2018.
El-Hattab AW, Schaaf CP, Fang P, Roeder E, Kimonis VE, Church JA, et al. ''Clinical characterization of int22h1/int22h2-mediated Xq28 duplication/deletion: new cases and literature review,'' BMC Med Genet, vol. 16, pp. 1-12 , Dec 2015.
Bianchi V, Farisello P, Baldelli P, Meskenaite V, Milanese M, Vecellio M, et al. ''Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic vesicle pools and short-term synaptic plasticity, and can be corrected by appropriate learning training,'' Hum Mol Genet, vol. 18, pp. 105-17, Jan 2009.
Yamamoto T, Shimojima K, Shimada S, Yokochi K, Yoshitomi S, Yanagihara K, et al. ''Clinical impacts of genomic copy number gains at Xq28,'' Hum Genome Var, vol. 1, pp. 1-6, July 2014.
Vanmarsenille L, Giannandrea M, Fieremans N, Verbeeck J, Belet S, Raynaud M, et al. ''Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains,'' Hum Mutat, vol. 35, pp. 377-83, Mar 2014.
Vandewalle J, Van Esch H, Govaerts K, Verbeeck J, Zweier C, Madrigal I, et al. ''Dosage-dependent severity of the phenotype in patients with mental retardation due to a recurrent copy-number gain at Xq28 mediated by an unusual recombination,'' Am J Hum Genet, vol. 85, pp. 809-22, Dec 2009.
Ward DI, Buckley BA, Leon E, Diaz J, Galegos MF, Hofherr S, et al. ''Intellectual disability and epilepsy due to the K/L-mediated Xq28 duplication: Further evidence of a distinct, dosage-dependent phenotype,'' Am J Med Genet A, vol. 176, pp. 551-9, Mar 2018.
Rivero F, Illenberger D, Somesh BP, Dislich H, Adam N, Meyer A-K. ''Defects in cytokinesis, actin reorganization and the contractile vacuole in cells deficient in RhoGDI,'' EMBO J, vol. 21, pp. 4539-49, Sep 2002.
Wüst RC, Degens H. ''Factors contributing to muscle wasting and dysfunction in COPD patients,'' Int J Chron Obstruct Pulmon Dis, vol. 2, pp. 289-300, Sep 2007.
Kim HC, Mofarrahi M, Hussain SN. ''Skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease,'' Int J Chron Obstruct Pulmon Dis, vol. 3, pp. 637-58, Dec 2008.
Jaitovich A, Barreiro E. ''Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease. What We Know and Can Do for Our Patients,'' Am J Respir Crit Care Med, vol. 198, pp. 175-86, Jul 2018.
Chen J, Gao F, Liu N. ''L1CAM promotes epithelial to mesenchymal transition and formation of cancer initiating cells in human endometrial cancer,'' Exp Ther Med, vol. 15, pp. 2792-7, Mar 2018.
Yu H, Zhou P, Li D, Li W. ''L1CAM-positive expression is associated with poorer survival outcomes in resected non-small cell lung cancer patients,'' Int J Clin Exp Pathol, vol. 12, pp. 2665-72, Jul 2019.
Stolz D, Meyer A, Rakic J, Boeck L, Scherr A, Tamm M. ''Mortality risk prediction in COPD by a prognostic biomarker panel,'' Eur Respir J, vol. 44, pp. 1557-70, Dec 2014.
de Leeuw PW, Dees A. ''Fluid homeostasis in chronic obstructive lung disease,'' Eur Respir J, vol. 22, pp. 33s-40s, Nov 2003.
Sarkar M, Bhardwaz R, Madabhavi I, Modi M. ''Physical signs in patients with chronic obstructive pulmonary disease,'' Lung India Off Organ Indian Chest Soc, vol. 36, pp. 38-47, Feb 2019.
Dasari S, Ganjayi MS, Meriga B. ''Glutathione S-transferase is a good biomarker in acrylamide induced neurotoxicity and genotoxicity,'' Interdiscip Toxicol, vol. 11, pp. 115-21, Aug 2018.
Yuan C, Chang D, Lu G, Deng X. ''Genetic polymorphism and chronic obstructive pulmonary disease,'' Int J Chron Obstruct Pulmon Dis, vol. 12, pp. 1385-93, May 2017.
Imboden M, Downs SH, Senn O, Matyas G, Brändli O, Russi EW, et al. ''Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study,'' Respir Res, vol. 8, Jan 2007.
Rogers AJ, Brasch-Andersen C, Ionita-Laza I, Murphy A, Sharma S, Klanderman BJ, et al. ''The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma,'' Clin Exp Allergy J Br Soc Allergy Clin Immunol,'' vol. 39, pp. 1721-9, Nov 2009.
Dey T, Gogoi K, Unni BG, Kalita M, Bharadwaz M, Bhattacharjee M, et al. ''Role of Glutathione S Transferase Polymorphism in COPD with Special Reference to Peoples Living in the Vicinity of the Open Cast Coal Mine of Assam,'' PLoS ONE, vol. 9, pp. e96739, May 2014.
Cao T, Xu N, Wang Z, Liu H. ''Effects of Glutathione S-Transferase Gene Polymorphisms and Antioxidant Capacity per Unit Albumin on the Pathogenesis of Chronic Obstructive Pulmonary Disease,'' Oxid Med Cell Longev, vol. 2017, Aug 2017.
Kim S-J, Kim M-G, Kim K-S, Song J-S, Yim S-V, Chung J-H. ''Impact of Glutathione S-Transferase M1 and T1 Gene Polymorphisms on the Smoking-Related Coronary Artery Disease,'' J Korean Med Sci, vol. 23, pp. 365-72, Jun 2008.
Witkos TM, Lowe M. ''The Golgin Family of Coiled-Coil Tethering Proteins,'' Front Cell Dev Biol, vol. 3, pp. 86, Jan 2016.
Antonacci F, Dennis MY, Huddleston J, Sudmant PH, Steinberg KM, Rosenfeld JA, et al. ''Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability,'' Nat Genet, vol. 46, pp. 1293-302, Dec 2014.
Matouk IJ, Halle D, Gilon M, Hochberg A. ''The non-coding RNAs of the H19-IGF2 imprinted loci: A focus on biological roles and therapeutic potential in Lung Cancer,'' J Transl Med, vol. 13, pp. 113, Apr 2015.
Lewis A, Lee JY, Donaldson AV, Natanek SA, Vaidyanathan S, Man WD ‐C., et al. ''Increased expression of H19/miR‐675 is associated with a low fat‐free mass index in patients with COPD,'' J Cachexia Sarcopenia Muscle, vol. 7, pp. 330-44, Jun 2016.
Than BLN, Goos JACM, Sarver AL, O’Sullivan MG, Rod A, Starr TK, et al. ''The role of KCNQ1 in mouse and human gastrointestinal cancers,'' Oncogene, vol. 33, pp. 3861-8, Jul 2014.
Unoki H, Takahashi A, Kawaguchi T, Hara K, Horikoshi M, Andersen G, et al. ''SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations,'' Nat Genet, vol. 40, pp. 1098-102, Sep 2008.
Ligthart S, Steenaard RV, Peters MJ, van Meurs JBJ, Sijbrands EJG, Uitterlinden AG, et al. ''Tobacco smoking is associated with DNA methylation of diabetes susceptibility genes,'' Diabetologia, vol. 59, pp. 998-1006, Jan 2016.
Tsaprouni LG, Yang T-P, Bell J, Dick KJ, Kanoni S, Nisbet J, et al. ''Cigarette smoking reduces DNA methylation levels at multiple genomic loci but the effect is partially reversible upon cessation,'' Epigenetics, vol. 9, pp. 1382-96, Oct 2014.
Bartoszewski R, Matalon S, Collawn JF. ''Ion channels of the lung and their role in disease pathogenesis,'' Am J Physiol - Lung Cell Mol Physiol, vol. 313, pp. L859-72, Nov 2017.
Malerba M, Montuschi P, Radaeli A, Pirisi M. ''Role of beta-blockers in patients with COPD: current perspective,'' Drug Discov Today, vol. 20, pp. 129-35, Jan 2015.
Pelaia G, Vatrella A, Busceti MT, Gallelli L, Calabrese C, Terracciano R, et al. ''Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma,'' Mediators Inflamm, vol. 2015, Mar 2015.
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