Skip to main content
SpringerLink
Log in

Genetic Polymorphisms of Cytochrome P450 and Matrix Metalloproteinase in Chronic Obstructive Pulmonary Disease

  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

We investigated whether polymorphisms of cytochrome P450 (CYP) and matrix metalloproteinase (MMP) are associated with the development and severity of chronic obstructive pulmonary disease (COPD). Genotypes of 184 patients with COPD and 212 controls were determined by polymerase chain reaction, followed by restriction fragment length polymorphism. The homozygous T allele of MMP-9 was significantly higher in patients with COPD than in controls (14.7% vs. 7.5%). The odds ratio was 2.4 (95% CI 1.1–5.9). No differences were observed in the frequency of polymorphic genotypes in CYP1A1, 1A2, MMP-1 and -3. During combined analysis of these candidate genes, we found strong indicators for susceptibility to COPD (combined with homozygotes *2A for CYP1A1 and T alleles of MMP-9 versus others = 3.3, 95% CI 1.2–8.6). The frequency of the homozygous *2A allele of CYP1A1 was significantly higher in very severe COPD (P < 0.01). Combinations of genetic variants including *2A homozygotes of CYP1A1 and T alleles in MMP-9 are significant indicators for susceptibility to COPD. The homozygous *2A allele of CYP1A1 is an independent risk factor for very severe COPD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bascom R (1991) Differential susceptibility to tobacco smoke: possible mechanisms. Pharmacogenetics 1:102–106

    Article  PubMed  CAS  Google Scholar 

  • Cantlay AM, Lamb D, Gillooly M, Norrman J, Morrison D, Smith CA, Harrison DJ (1995) Association between the CYP1A1 gene polymorphism and susceptibility to emphysema and lung cancer. Clin Mol Pathol 48(4):M210–M214

    Article  PubMed  CAS  Google Scholar 

  • Cascorbi I, Brockmoller J, Roots I (1996) A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkage, and impact on lung cancer susceptibility. Cancer Res 56:4965–4969

    PubMed  CAS  Google Scholar 

  • Chida M, Yokoi T, Fukui T, Kinoshita M, Yokota J, Kamataki T (1999) Detection of three genetic polymorphisms in the 5′ flanking region and intron 1 of human CYP1A2 in Japanese population. Jpn J Cancer Res 90(9):899–902

    PubMed  CAS  Google Scholar 

  • Crews ST, Fan CM (1999) Remembrance of things PAS, regulation of development by bHLH-PAS protein. Curr Opin Genet Dev 9:580–587

    Article  PubMed  CAS  Google Scholar 

  • D’Armiento J, Dalal SS, Okada Y, Berg RA, Chada K (1992) Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema. Cell 71(6):955–961

    Article  PubMed  Google Scholar 

  • Dunleavey L, Beyzade S, Ye S (2000a) Rapid genotype analysis of the matrix metalloproteinase-1 gene 1G/2G polymorphism that is associated with risk of cancer. Matrix Biol 19:175–177

    Article  PubMed  CAS  Google Scholar 

  • Dunleavey L, Beyzade S, Ye S (2000b) Rapid genotype analysis of the stromelysin gene 5A/6A polymorphism. Atherosclerosis 151:587–589

    Article  PubMed  CAS  Google Scholar 

  • Finlay GA, O’Driscoll LR, Russell KJ, D’Arcy EM, Masterson JB, FitzGerald MX, O’Connor CM (1997a) Matrix metalloproteinase expression by alveolar macrophages in emphysema. Am J Respir Crit Care Med 156(1):240–247

    PubMed  CAS  Google Scholar 

  • Finlay GA, Russell KJ, McMahon KJ, D’arcy EM, Masterson JB, FitzGerald MX, O’Connor CM (1997b) Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients. Thorax 52(6):502–506

    Article  PubMed  CAS  Google Scholar 

  • Fletcher C, Peto R (1977) The natural history of chronic airway obstruction. Br Med J 25:1645–1648

    Article  Google Scholar 

  • Fujii-Juriyama Y, Imataka H, Sogawa K, Yasumoto K, Kikuchi Y (1992) Regulation of CYP1A1 expression. FASEB J 6(2):706–710

    Google Scholar 

  • Hong YS, Chang JH, Kwon OJ, Ham YA, Choi JH (1998) Polymorphism of the CYP1A1 and glutathione S-transferase gene in Korean lung cancer patients. Exp Mol Med 30(4):192–198

    PubMed  CAS  Google Scholar 

  • Imai K, Dalal SS, Chen ES, Downey R, Schulman LL, Ginsburg M, D’Armiento J (2001) Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema. Am J Respir Crit Care Med 163:786–791

    PubMed  CAS  Google Scholar 

  • Ito I, Nagai S, Handa T, Muro S, Hirai T, Tsukino M, Mishima M (2005) Matrix metalloproteinase-9 promoter polymorphism associated with upper lung dominant emphysema. Am J Respir Crit Care Med 172(11):1378–1382

    Article  PubMed  Google Scholar 

  • Joos L, He JQ, Shepherdson MB, Connett JE, Anthonisen NR, Pare PD, Sandford AJ (2002) The role of matrix metalloproteinase polymorphisms in the rate of decline in lung function. Hum Mol Genet 11(5):569–576

    Article  PubMed  CAS  Google Scholar 

  • Khoury MJ, Beaty TH, Newill CA, Bryant S, Cohen BH (1986) Genetic environmental interactions in chronic airways obstruction. Int J Epidemiol 15(1):65–72

    Article  PubMed  CAS  Google Scholar 

  • Kueppers F, Miller RD, Gordon H, Hepper NG, Offord K (1977) Familial prevalence of chronic obstructive pulmonary disease in a matched pair study. Am J Med 63(3):336–342

    Article  PubMed  CAS  Google Scholar 

  • Kuppers F, Black LF (1974) Alpha 1-antitrypsin and its deficiency. Am Rev Respir Dis 110:176–194

    Google Scholar 

  • Landi MT, Bertazzi PA, Shields PG, Clark G, Lucier GW, Garte SJ, Cosma G, Caporaso NE (1994) Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans. Pharmacogenetics 4(5):242–246

    Article  PubMed  CAS  Google Scholar 

  • Laurell CC, Eriksson S (1963) The electrophoretic α1-globulin pattern of serum in α1-antitrypsin deficiency. Scand J Clin Lab Invest 15:132–140

    Article  CAS  Google Scholar 

  • Le Marchand L, Sivaraman L, Pierce L, Seifried A, Lum A, Wilkens LR, Lau AF (1998) Association of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens. Cancer Res 58(21):4858–4863

    PubMed  CAS  Google Scholar 

  • McCloskey SC, Patel BD, Hinchliffe SJ, Reid ED, Wareham NJ, Lomas DA (2001) Siblings of patients with severe chronic obstructive pulmonary disease have a significant risk of airway obstruction. Am J Respir Crit Care Med 164:1419–1424

    PubMed  CAS  Google Scholar 

  • Minematsu N, Nakamura H, Tateno H, Nakajima T, Yamaguchi K (2001) Genetic polymorphism in matrix metalloproteinase-9 and pulmonary emphysema. Biochem Biophys Res Commun 289(1):116–119

    Article  PubMed  CAS  Google Scholar 

  • Murphy KA, Villano CM, Dorn R, White LA (2004) Interaction between the aryl hydrocarbon receptor and retinoic acid pathways increases matrix metaoolproteinase-1 expression in keratinocytes. J Biol Chem 279(24):25284–25293

    Article  PubMed  CAS  Google Scholar 

  • Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J. Biol. Chem 274(31):21491–21494

    Article  PubMed  CAS  Google Scholar 

  • Nerurkar PV, Okinaka L, Aoki C, Seifried A, Lum-Jones A, Wilkens LR, Le Marchand L (2000) CYP1A1, GSTM1, and GSTP1 genetic polymorphisms and urinary 1-hydroxypyrene excretion in non-occupationally exposed individuals. Cancer Epidemiol Biomarkers Prev 9(10):1119–1122

    PubMed  CAS  Google Scholar 

  • Nihlen U, Nyberg P, Montnemery P, Lofdahl CG (2004) Influence of family history and smoking habits on the incidence of self-reported physician’s diagnosis of COPD. Respir Med 98(3):263–270

    Article  PubMed  Google Scholar 

  • Ohnoshi K, Takagi M, Kurokawa Y, Satomi S, Konttinen YT (1998) Matrix metalloproteinase-mediated extracellular matrix protein degradation in human pulmonary emphysema. Lab Invest 78(9):1077–1087

    Google Scholar 

  • Sachse C, Brockmoller J, Bauer S, Roots I (1997) Functional significance of a C→A polymorphism in intron 1 of the cytochrome P450 1A2 (CYP1A2) gene tested with caffeine. B J Clin Pharmacol 47(4):445–449

    Article  Google Scholar 

  • Samnegard A, Silveira A, Lundman P, Boquist S, Odeberg J, Hulthe J, McPheat W, Tornvall P, Berqstrand L, Ericsson CG, Hamsten A, Eriksson P (2005) Serum matrix metalloproteinase-3 concentration is influenced by MMP-3-1612 5A/6A promoter genotype and associated with myocardial infarction. J Intern Med 258(5):411–419

    Article  PubMed  CAS  Google Scholar 

  • Segura-Valdez L, Pardo A, Gaxiola M, Uhal BD, Becerril C, Selman M (2000) Upregulation of gelatinases A and B, collagenase 1 and 2, and increased parenchymal cell death in COPD. Chest 117(3):684–694

    Article  PubMed  CAS  Google Scholar 

  • Sobti RC, Sharma S, Joshi A, Jindal SK, Janmeja A (2004) Genetic polymorphism of the CYP1A1, CYP2E1, GSTM1 and GSTT1 genes and lung cancer susceptibility in a north indian population. Mol Cell Biochem 266(1–2):1–9

    Article  PubMed  CAS  Google Scholar 

  • Villano CM, Murphy KA, Akintobi A, White LA (2006) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells. Toxicol Appl Pharmacol 210(3):212–224

    Article  PubMed  CAS  Google Scholar 

  • Vineis P, Veglia F, Anttila S, Benhamou S, Clapper ML, Dolzan V, Ryberg D, Hirvonen A, Kremers P, Le Marchand L, Pastorelli R, Rannug A, Romkes M, Schoket B, Strange RC, Garte S, Taioli E (2004) CYP1A1, GSTM1 and GSTT1 polymorphisms and lung cancer: a pooled analysis of gene–gene interactions. Biomarkers 9(3):298–305

    Article  PubMed  CAS  Google Scholar 

  • Ye S (2000) Polymorphism in matrix metalloproteinase gene promoters: implication in regulation of gene expression and susceptibility of various diseases. Matrix Biol 19:623–629

    Article  PubMed  CAS  Google Scholar 

  • Zhang B, Ye S, Herrmann SM, Eriksson P, de Maat M, Evans A, Arveiler D, Luc G, Cambien F, Hamsten A, Watkins H, Henney AM (1999) Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis. Circulation 99(14):1788–1794

    PubMed  CAS  Google Scholar 

  • Zhou M, Huang SG, Wan HY, Li B, Deng WW, Li M (2004) Genetic polymorphism in matrix metalloproteinase-9 and the susceptibility to chronic obstructive pulmonary disease in Han population of south China. Chin Med J (Engl) 117(10):1481–1484

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan

    Shih-Lung Cheng

  2. Department of Chemical Engineering and Materials Science, Yuan-Ze University, Taoyuan, Taiwan

    Shih-Lung Cheng

  3. Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, No. 7, Chung-Shan South Road, Taipei, Taiwan

    Shih-Lung Cheng, Chong-Jen Yu & Pan-Chyr Yang

Authors
  1. Shih-Lung Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chong-Jen Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pan-Chyr Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chong-Jen Yu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, SL., Yu, CJ. & Yang, PC. Genetic Polymorphisms of Cytochrome P450 and Matrix Metalloproteinase in Chronic Obstructive Pulmonary Disease. Biochem Genet 47, 591–601 (2009). https://doi.org/10.1007/s10528-009-9252-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-009-9252-4

Keywords

Search

Navigation