Updates on the COPD gene list

A genetic contribution to develop chronic obstructive pulmonary disease (COPD) is well established. However, the specific genes responsible for enhanced risk or host differences in susceptibility to smoke exposure remain poorly understood. The goal of this review is to provide a comprehensive literature overview on the genetics of COPD, highlight the most promising findings during the last few years, and ultimately provide an updated COPD gene list. Candidate gene studies on COPD and related phenotypes indexed in PubMed before January 5, 2012 are tabulated. An exhaustive list of publications for any given gene was looked for. This well-documented COPD candidate-gene list is expected to serve many purposes for future replication studies and meta-analyses as well as for reanalyzing collected genomic data in the field. In addition, this review summarizes recent genetic loci identified by genome-wide association studies on COPD, lung function, and related complications. Assembling resources, integrative genomic approaches, and large sample sizes of well-phenotyped subjects is part of the path forward to elucidate the genetic basis of this debilitating disease.

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[49]  Yun Feng,et al.  Lack of Association Between the TGF-β1 Gene and Development of COPD in Asians: A Case–Control Study and Meta-analysis , 2011, Lung.

[50]  R. Bowler,et al.  Superoxide dismutase 3 polymorphism associated with reduced lung function in two large populations. , 2008, American journal of respiratory and critical care medicine.

[51]  D. Christiani,et al.  Lack of Associations Between Several Polymorphisms in Cytokine Genes and the Risk of Chronic Obstructive Pulmonary Diseases in Taiwan , 2008, The Kaohsiung journal of medical sciences.

[52]  W James Gauderman,et al.  Effects of glutathione-S-transferase M1, T1, and P1 on childhood lung function growth. , 2002, American journal of respiratory and critical care medicine.

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[54]  E. Silverman,et al.  Association of vitamin D receptor gene polymorphisms with childhood and adult asthma. , 2004, American journal of respiratory and critical care medicine.

[55]  K. Sekizawa,et al.  CLCA1 gene polymorphisms in chronic obstructive pulmonary disease , 2004, Journal of Medical Genetics.

[56]  M. Spiroski,et al.  Association of cytokine gene polymorphisms with chronic obstructive pulmonary disease in Macedonians. , 2009, Iranian journal of allergy, asthma, and immunology.

[57]  M. Miravitlles,et al.  Detection of polymorphisms at exons 3 (Tyr113-->His) and 4 (His139-->Arg) of the microsomal epoxide hydrolase gene using fluorescence PCR method combined with melting curves analysis. , 2002, Analytical biochemistry.

[58]  P. Ran,et al.  Association between polymorphisms of microsomal epoxide hydrolase and COPD: Results from meta‐analyses , 2008, Respirology.

[59]  K. Sekizawa,et al.  Association analysis of tissue inhibitor of metalloproteinase2 gene polymorphisms with COPD in Egyptians. , 2005, Respiratory medicine.

[60]  S. Yao,et al.  Association of Vitamin D Binding Protein Variants with Susceptibility to Chronic Obstructive Pulmonary Disease , 2010, The Journal of international medical research.

[61]  I. Sayers,et al.  The role of LTA4H and ALOX5AP polymorphism in asthma and allergy susceptibility , 2008, Allergy.

[62]  N. Anthonisen,et al.  Association of Hck genetic polymorphisms with gene expression and COPD , 2006, Human Genetics.

[63]  G. Mills,et al.  Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1 , 2008, Nature Genetics.

[64]  Huahao Shen,et al.  Association between polymorphism of glutathione S-transferase P1 and chronic obstructive pulmonary disease: a meta-analysis. , 2010, Respiratory medicine.

[65]  E. Bleecker,et al.  The glucocorticoid receptor heterocomplex gene STIP1 is associated with improved lung function in asthmatic subjects treated with inhaled corticosteroids. , 2009, The Journal of allergy and clinical immunology.

[66]  R. Abboud,et al.  Effect of heme oxygenase-1 polymorphisms on lung function and gene expression , 2011, BMC Medical Genetics.

[67]  C. Smith,et al.  Association between the CYP1A1 gene polymorphism and susceptibility to emphysema and lung cancer , 1995, Clinical molecular pathology.

[68]  A. Gemma,et al.  Association of serotonin transporter gene variation with smoking, chronic obstructive pulmonary disease, and its depressive symptoms , 2011, Journal of Human Genetics.

[69]  M. Abramson,et al.  Microsomal Epoxide Hydrolase Is Not Associated with COPD in a Community-Based Sample , 2006, Human biology.

[70]  Xia Li,et al.  Association between the tumour necrosis factor‐α−308G/A polymorphism and chronic obstructive pulmonary disease: An update , 2011, Respirology.

[71]  E. Silverman,et al.  Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease. , 2009, Human molecular genetics.

[72]  E. Silverman,et al.  Genetic Linkage and Association Analysis of COPD-Related Traits on Chromosome 8p , 2006, COPD.

[73]  H. Oflaz,et al.  Gene polymorphisms of endothelial nitric oxide synthase enzyme associated with pulmonary hypertension in patients with COPD. , 2003, Respiratory medicine.

[74]  S. Muro,et al.  Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema. , 2005, American journal of respiratory and critical care medicine.

[75]  L. Z. Akhmadishina,et al.  [Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan]. , 2006, Molekuliarnaia biologiia.

[76]  R. Tkacova,et al.  Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population. , 2008, Croatian medical journal.

[77]  Zhen-xiang Zhang,et al.  hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms associated with chronic obstructive pulmonary disease. , 2009, Chinese medical journal.

[78]  K. Morgan,et al.  A polymorphism in the tumor necrosis factor-alpha gene promoter region may predispose to a poor prognosis in COPD. , 2000, Chest.

[79]  A. Sastre,et al.  Alpha 1-antitrypsin Pi-types in 965 COPD patients. , 1986, Chest.

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[82]  P. Talmud,et al.  SERPINA1 11478G→A variant, serum α1-antitrypsin, exacerbation frequency and FEV1 decline in COPD , 2011, Thorax.

[83]  H. Boezen,et al.  Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts , 2011, Respiratory research.

[84]  M. Spitz,et al.  Deciphering the impact of common genetic variation on lung cancer risk: a genome-wide association study. , 2009, Cancer research.

[85]  H. Shirasawa,et al.  Vascular endothelial growth factor and the risk of smoking-related COPD. , 2003, Chest.

[86]  A. Chuchalin,et al.  Mis-sense mutation of alpha 1-antichymotrypsin gene and chronic lung disease. , 1993, The Lancet.

[87]  Matsui,et al.  Association between alpha‐1‐antichymotrypsin polymorphism and susceptibility to chronic obstructive pulmonary disease , 2000, European journal of clinical investigation.

[88]  E. Trabetti,et al.  CFTR gene variant IVS8-5T in disseminated bronchiectasis. , 1996, American journal of human genetics.

[89]  N. Pride,et al.  Tumour necrosis factor-alpha gene promoter polymorphism in chronic obstructive pulmonary disease. , 2000, The European respiratory journal.

[90]  E. Silverman,et al.  Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease , 2011, Thorax.

[91]  I. Tkáč,et al.  Glutathione S-transferase M1 gene polymorphism is related to COPD in patients with non-small-cell lung cancer , 2004, Wiener Klinische Wochenschrift.

[92]  Olaf Holz,et al.  Association of Tumor Necrosis Factor-α Polymorphisms and Ozone-induced Change in Lung Function , 2005 .

[93]  G. Lefranc,et al.  Combined Analysis of EPHX1, GSTP1, GSTM1 and GSTT1 Gene Polymorphisms in Relation to Chronic Obstructive Pulmonary Disease Risk and Lung Function Impairment , 2011, Disease markers.

[94]  A. Chuchalin,et al.  Mis-sense mutation of α1-antichymotrypsin gene and chronic lung disease , 1993, The Lancet.

[95]  Xiao-Dong Yang,et al.  Association of interleukin (IL)-12 and IL-27 gene polymorphisms with chronic obstructive pulmonary disease in a Chinese population. , 2008, DNA and cell biology.

[96]  Ying Wang,et al.  A genome-wide association study of lung cancer identifies a region of chromosome 5p15 associated with risk for adenocarcinoma. , 2009, American journal of human genetics.

[97]  Pan‐Chyr Yang,et al.  Genetic Polymorphisms of Cytochrome P450 and Matrix Metalloproteinase in Chronic Obstructive Pulmonary Disease , 2009, Biochemical Genetics.

[98]  B. Nordestgaard,et al.  Elevated ACE activity is not associated with asthma, COPD, and COPD co-morbidity. , 2009, Respiratory medicine.

[99]  C. Shih,et al.  Polymorphisms of p53 and p21 genes in chronic obstructive pulmonary disease. , 2006, The Journal of laboratory and clinical medicine.

[100]  Edwin K Silverman,et al.  Analysis of exonic elastin variants in severe, early-onset chronic obstructive pulmonary disease. , 2009, American journal of respiratory cell and molecular biology.

[101]  D. DeMeo,et al.  Xenobiotic metabolizing enzyme gene polymorphisms predict response to lung volume reduction surgery , 2007, Respiratory research.

[102]  M. Emi,et al.  A nonfunctioning single nucleotide polymorphism in olfactory receptor gene family is associated with the forced expiratory volume in the first second/the forced vital capacity values of pulmonary function test in a Japanese population. , 2007, Biochemical and biophysical research communications.

[103]  M. Athar,et al.  Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive pulmonary disease. , 2007, Clinica chimica acta; international journal of clinical chemistry.

[104]  Paolo Vineis,et al.  A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25 , 2008, Nature.

[105]  Morten Dahl,et al.  Change in Lung Function and Morbidity from Chronic Obstructive Pulmonary Disease in 1-Antitrypsin MZ Heterozygotes: A Longitudinal Study of the General Population , 2002, Annals of Internal Medicine.

[106]  F. Martinez,et al.  Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. , 2007, American journal of respiratory and critical care medicine.

[107]  D. Johns,et al.  β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults , 2006, Journal of Human Genetics.

[108]  W. Poller,et al.  DNA polymorphisms of the alpha 1-antitrypsin gene region in patients with chronic obstructive pulmonary disease. , 1990, European journal of clinical investigation.

[109]  H. Shirasawa,et al.  Association of tumor necrosis factor alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[110]  M. Selman,et al.  Surfactant protein gene A, B, and D marker alleles in chronic obstructive pulmonary disease of a Mexican population. , 2001, The European respiratory journal.

[111]  Sunita Ghosh,et al.  Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers , 2008, Pharmacogenetics and genomics.

[112]  Yong Song,et al.  TNF-308 gene polymorphism is associated with COPD risk among Asians: meta-analysis of data for 6,118 subjects , 2010, Molecular Biology Reports.

[113]  R. Bowler,et al.  Polymorphisms in the Superoxide Dismutase-3 Gene Are Associated with Emphysema in COPD , 2010, COPD.

[114]  K. Morgan,et al.  Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD , 2008, European Respiratory Journal.

[115]  D. Heine-Suñer,et al.  Angiotensin-converting-enzyme gene polymorphisms, smoking and chronic obstructive pulmonary disease , 2007, International journal of chronic obstructive pulmonary disease.

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[120]  Association between candidate genes and lung function growth in Chinese asthmatic children , 2007, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

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[122]  W. Yew,et al.  Protease inhibitor phenotypes and serum alpha‐1‐antitrypsin levels in patients with COPD: A study from Hong Kong , 2004, Respirology.

[123]  S. Muro,et al.  Risk and severity of COPD is associated with the group-specific component of serum globulin 1F allele. , 2004, Chest.

[124]  I. Sayers,et al.  PLAUR polymorphisms and lung function in UK smokers , 2009, BMC Medical Genetics.

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[126]  N. Anthonisen,et al.  Polymorphisms of interleukin-10 and its receptor and lung function in COPD , 2007, European Respiratory Journal.

[127]  B. Make,et al.  Candidate genes for COPD in two large data sets , 2010, European Respiratory Journal.

[128]  M. Hasegawa,et al.  Functional single nucleotide polymorphisms of the CCL5 gene and nonemphysematous phenotype in COPD patients , 2008, European Respiratory Journal.

[129]  L. Edwards,et al.  A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13. , 2012, Human molecular genetics.

[130]  T. Pietras,et al.  The sequence polymorphism of MnSOD gene in subjects with respiratory insufficiency in COPD. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[131]  A. Gillissen,et al.  Angiotensin-converting enzyme I/D polymorphism in chronic obstructive pulmonary disease , 2009, European journal of medical research.

[132]  Inês Barroso,et al.  Genome-wide association study identifies five loci associated with lung function , 2010, Nature Genetics.

[133]  K. Morgan,et al.  The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study , 2011, BMC Medical Genetics.

[134]  B. Mittal,et al.  Association of Genetic Polymorphism of GSTT1, GSTM1 and GSTM3 in COPD Patients in a North Indian Population , 2011, COPD.

[135]  Zhen-xiang Zhang,et al.  Correlation of HDEFB1 polymorphism and susceptibility to chronic obstructive pulmonary disease in Chinese Han population. , 2004, Chinese medical journal.

[136]  Cleo C. van Diemen,et al.  A Disintegrin and Metalloprotease 33 polymorphisms and lung function decline in the general population , 2006, European Respiratory Review.

[137]  A. Hofman,et al.  C-reactive protein levels, haplotypes, and the risk of incident chronic obstructive pulmonary disease. , 2009, American journal of respiratory and critical care medicine.

[138]  K. Sekizawa,et al.  Tissue inhibitor of metalloproteinases-2 gene polymorphisms in chronic obstructive pulmonary disease. , 2001, The European respiratory journal.

[139]  E. Silverman,et al.  Polymorphisms in surfactant protein-D are associated with chronic obstructive pulmonary disease. , 2011, American journal of respiratory cell and molecular biology.

[140]  M. Schwarz,et al.  TGF-β1 genotype and accelerated decline in lung function of patients with cystic fibrosis , 2000, Thorax.

[141]  Edwin K Silverman,et al.  Transforming growth factor-beta receptor-3 is associated with pulmonary emphysema. , 2009, American journal of respiratory cell and molecular biology.

[142]  B. Nordestgaard,et al.  Genetically increased antioxidative protection and decreased chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

[143]  A. Uslu,et al.  The effect of CYP1A2 gene polymorphisms on Theophylline metabolism and chronic obstructive pulmonary disease in Turkish patients. , 2010, BMB reports.

[144]  D. Gottlieb,et al.  Secreted modular calcium-binding protein 2 haplotypes are associated with pulmonary function. , 2007, American journal of respiratory and critical care medicine.

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[146]  I. Kubota,et al.  A novel polymorphism in CDC6 is associated with the decline in lung function of ex-smokers in COPD. , 2009, Biochemical and biophysical research communications.

[147]  M. V. van Krugten,et al.  Tumor Necrosis Factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease , 2002, Respiratory research.

[148]  I. Kubota,et al.  Intronic single‐nucleotide polymorphisms in Bcl‐2 are associated with chronic obstructive pulmonary disease severity , 2007, Respirology.

[149]  S. Chanock,et al.  PTEN identified as important risk factor of chronic obstructive pulmonary disease. , 2009, Respiratory medicine.

[150]  L. Palmer,et al.  β2 adrenoceptor Arg16Gly polymorphism, airway responsiveness, lung function and asthma in infants and children , 2004 .

[151]  E. Wouters,et al.  Chronic obstructive pulmonary disease is associated with the -1055 IL-13 promoter polymorphism , 2002, Genes and Immunity.

[152]  Christoph Lange,et al.  The SERPINE2 gene is associated with chronic obstructive pulmonary disease. , 2006, American journal of human genetics.

[153]  C. Gieger,et al.  Sequence variants at CHRNB3–CHRNA6 and CYP2A6 affect smoking behavior , 2010, Nature Genetics.

[154]  M. Tzetis,et al.  CFTR gene mutations – including three novel nucleotide substitutions – and haplotype background in patients with asthma, disseminated bronchiectasis and chronic obstructive pulmonary disease , 2001, Human Genetics.

[155]  Ya-ping Zhang,et al.  Relationship between COPD and polymorphisms of HOX-1 and mEPH in a Chinese population. , 2007, Oncology reports.

[156]  J. Celedón,et al.  Association of VEGF polymorphisms with childhood asthma, lung function and airway responsiveness , 2009, European Respiratory Journal.

[157]  Marc Decramer,et al.  The 15q24/25 susceptibility variant for lung cancer and chronic obstructive pulmonary disease is associated with emphysema. , 2010, American journal of respiratory and critical care medicine.

[158]  J. Moss,et al.  Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha1-antitrypsin deficiency. , 1999, American journal of respiratory cell and molecular biology.

[159]  M. Yamakido,et al.  Microsomal epoxide hydrolase genotypes and chronic obstructive pulmonary disease in Japanese. , 2000, International journal of molecular medicine.

[160]  Weibo Liang,et al.  CTLA4 and CD86 gene polymorphisms and susceptibility to chronic obstructive pulmonary disease. , 2010, Human immunology.

[161]  A. Gulsvik,et al.  Genetic association between COPD and polymorphisms in TNF, ADRB2 and EPHX1 , 2006, European Respiratory Journal.

[162]  Edwin K Silverman,et al.  Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema. , 2011, American journal of respiratory and critical care medicine.

[163]  J. S. Kim,et al.  Polymorphisms in the type IV collagen α3 gene and the risk of COPD , 2008, European Respiratory Journal.

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[165]  P. Boelle,et al.  Glucocorticoid receptor gene polymorphisms associated with progression of lung disease in young patients with cystic fibrosis , 2007, Respiratory research.

[166]  Christian Gieger,et al.  Genome-wide association and large scale follow-up identifies 16 new loci influencing lung function , 2011, Nature Genetics.

[167]  Ya-ping Zhang,et al.  Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study , 2009, BMC Medical Genetics.

[168]  E. D. Yanchina,et al.  Gene-Gene Interactions between Glutathione-S Transferase M1 and Matrix Metalloproteinase 9 in the Formation of Hereditary Predisposition to Chronic Obstructive Pulmonary Disease , 2004, Bulletin of Experimental Biology and Medicine.

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[170]  M. Al-Rabia,et al.  Association and preferential transmission of the CCR2V64I polymorphism with absence of asthma in high-risk families. , 2008, Saudi medical journal.

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[173]  N. Kalsheker,et al.  Matrix metalloproteinase-12 (MMP-12) SNP affects MMP activity, lung macrophage infiltration and protects against emphysema in COPD , 2011, Thorax.

[174]  S. V. Von Essen,et al.  Polymorphisms in the CD14 gene associated with pulmonary function in farmers. , 2005, American journal of respiratory and critical care medicine.

[175]  S. Kudoh,et al.  Contribution of HLA genes to genetic predisposition in diffuse panbronchiolitis. , 1998, American journal of respiratory and critical care medicine.

[176]  B. Leynaert,et al.  ETB receptor polymorphism is associated with airway obstruction , 2007, BMC pulmonary medicine.

[177]  A. Tomovic,et al.  The CFTR M470V gene variant as a potential modifier of COPD severity: study of Serbian population. , 2008, Genetic testing.

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