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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2011

Open Access 01-12-2011 | Case control study

SERPINE2 haplotype as a risk factor for panlobular type of emphysema

Authors: Mari K Kukkonen, Emmi Tiili, Satu Hämäläinen, Tapio Vehmas, Panu Oksa, Päivi Piirilä, Ari Hirvonen

Published in: BMC Medical Genetics | Issue 1/2011

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Abstract

Background

SERPINE2 (serpin peptidase inhibitor, clade E, member 2) has previously been identified as a positional candidate gene for chronic obstructive pulmonary disease (COPD) and has subsequently been associated to COPD and emphysema in several populations. We aimed to further examine the role of SERPINE2 polymorphisms in the development of pulmonary emphysema and different emphysema subtypes.

Methods

Four single nucleotide polymorphisms (SNPs) in SERPINE2 were analyzed from 951 clinically and radiologically examined Finnish construction workers. The genotype and haplotype data was compared to different emphysematous signs confirmed with high-resolution computed tomography (HRCT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusing capacity (DLCO), and specific diffusing capacity (DLCO/VA).

Results

Three of the studied SERPINE2 SNPs (rs729631, rs975278, and rs6748795) were found to be in tight linkage disequilibrium. Therefore, only one of these SNPs (rs729631) was included in the subsequent analyses, in addition to the rs840088 SNP which was in moderate linkage with the other three studied SNPs. The rs729631 SNP showed a significant association with panlobular emphysema (p = 0.003). In further analysis, the variant allele of the rs729631 SNP was found to pose over two-fold risk (OR 2.22, 95% CI 1.05-4.72) for overall panlobular changes and over four-fold risk (OR 4.37, 95% CI 1.61-11.86) for pathological panlobular changes. A haplotype consisting of variant alleles of both rs729631 and rs840088 SNPs was found to pose an almost four-fold risk for overall panlobular (OR 3.72, 95% CI 1.56-8.90) and subnormal (OR 3.98, 95% CI 1.55-10.20) emphysema.

Conclusions

Our results support the previously found association between SERPINE2 polymorphisms and pulmonary emphysema. As a novel finding, our study suggests that the SERPINE2 gene may in particular be involved in the development of panlobular changes, i.e., the same type of changes that are involved in alpha-1-antitrypsin (AAT) -deficiency.
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Literature
1.
Barnes PJ: Chronic obstructive pulmonary disease. N Engl J Med. 2000, 343: 269-280. 10.1056/NEJM200007273430407.CrossRefPubMed
2.
Laurell CB, Eriksson S: The electrophoretic alpha-1-globulin pattern of serum in alpha-1-antirtypsin deficiency. Scand J Clin Invest. 1963, 15: 132-140.CrossRef
3.
Tomashefski JF, Crystal RG, Wiedemann HP, Mascha E, Stoller JK: The bronchopulmonary pathology of alpha-1 antitrypsin (AAT) deficiency: findings of the Death Review Committee of the national registry for individuals with Severe Deficiency of Alpha-1 Antitrypsin. Hum Pathol. 2004, 35: 1452-1461. 10.1016/j.humpath.2004.08.013.CrossRefPubMed
4.
Barnes PJ, Shapiro SD, Pauwels RA: Chronic obstructive pulmonary disease: molecular and cellular mechanisms. Eur Respir J. 2003, 22: 672-688. 10.1183/09031936.03.00040703.CrossRefPubMed
5.
Abboud RT, Vimalanathan S: Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema. Int J Tuberc Lung Dis. 2008, 12: 361-367.PubMed
6.
DeMeo D, Mariani T, Lange C, Lake S, Litonjua A, Celedon J, Reilly J, Chapman HA, Sparrow D, Spira A, et al: The SERPINE2 gene is associated with chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006, 3: 502-10.1513/pats.200603-070MS.CrossRefPubMed
7.
Zhu G, Warren L, Aponte J, Gulsvik A, Bakke P, Anderson WH, Lomas DA, Silverman EK, Pillai SG: The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations. Am J Respir Crit Care Med. 2007, 176: 167-173. 10.1164/rccm.200611-1723OC.CrossRefPubMed
8.
Cha SI, Kang HG, Choi JE, Kim MJ, Park J, Lee WK, Kim CH, Jung TH, Park JY: SERPINE2 polymorphisms and chronic obstructive pulmonary disease. J Korean Med Sci. 2009, 24: 1119-1125. 10.3346/jkms.2009.24.6.1119.CrossRefPubMedPubMedCentral
9.
Chappell S, Daly L, Morgan K, Baranes TG, Roca J, Rabinovich R, Millar A, Donnelly SC, Keatings V, MacNee W, et al: The SERPINE2 gene and chronic obstructive pulmonary disease. Am J Hum Genet. 2006, 79: 184-186. 10.1086/505268. author reply 186-187CrossRefPubMedPubMedCentral
10.
Zhong L, Fu WP, Sun C, Dai LM, Zhang YP: Absence of association between SERPINE2 genetic polymorphisms and chronic obstructive pulmonary disease in Han Chinese: a case-control cohort study. BMC Med Genet. 2009, 10: 66-CrossRefPubMedPubMedCentral
11.
Kim WJ, Hoffman E, Reilly J, Hersh C, Demeo D, Washko G, Silverman EK: Association of COPD candidate genes with CT emphysema and airway phenotypes in severe COPD. Eur Respir J. 2010, 37: 39-43.CrossRefPubMedPubMedCentral
12.
Fujimoto K, Ikeda S, Arai T, Tanaka N, Kumasaka T, Ishii T, Kida K, Muramatsu M, Sawabe M: Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases. BMC Med Genet. 11: 159-
13.
Huuskonen O, Kivisaari L, Zitting A, Kaleva S, Vehmas T: Emphysema findings associated with heavy asbestos-exposure in high resolution computed tomography of finnish construction workers. J Occup Health. 2004, 46: 266-271. 10.1539/joh.46.266.CrossRefPubMed
14.
Piirila P, Lindqvist M, Huuskonen O, Kaleva S, Koskinen H, Lehtola H, Vehmas T, Kivisaari L, Sovijarvi AR: Impairment of lung function in asbestos-exposed workers in relation to high-resolution computed tomography. Scand J Work Environ Health. 2005, 31: 44-51.CrossRefPubMed
15.
Vierikko T, Jarvenpaa R, Autti T, Oksa P, Huuskonen M, Kaleva S, Laurikka J, Kajander S, Paakkola K, Saarelainen S, et al: Chest CT screening of asbestos-exposed workers: lung lesions and incidental findings. Eur Respir J. 2007, 29: 78-84.CrossRefPubMed
16.
Webb W, Müller N, Naidich D: High-resolution CT of the lung. 1996, Philadelphia: Lippincott-Raven Publishers, 2
17.
Viljanen AA: Reference values for spirometric, pulmonary diffusing capacity and body plethysmographic studies. Scand J Clin Invest. 1982, 42 (suppl 159): 1-50.
18.
Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC: Lung volumes and forced ventilatory flows. Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993, 16: 5-40.CrossRefPubMed
19.
Cotes JE, Chinn DJ, Quanjer PH, Roca J, Yernault JC: Standardization of the measurement of transfer factor (diffusing capacity). Report Working Party Standardization of Lung Function Tests, European Community for Steel and Coal. Official Statement of the European Respiratory Society. Eur Respir J Suppl. 1993, 16: 41-52.CrossRefPubMed
20.
Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005, 21: 263-265. 10.1093/bioinformatics/bth457.CrossRefPubMed
21.
Stephens M, Smith NJ, Donnelly P: A new statistical method for haplotype reconstruction from population data. Am J Hum Genet. 2001, 68: 978-989. 10.1086/319501.CrossRefPubMedPubMedCentral
22.
23.
Dawkins PA, Dawkins CL, Wood AM, Nightingale PG, Stockley JA, Stockley RA: Rate of progression of lung function impairment in alpha1-antitrypsin deficiency. Eur Respir J. 2009, 33: 1338-1344. 10.1183/09031936.00061208.CrossRefPubMed
24.
Baker JB, Low DA, Simmer RL, Cunningham DD: Protease-nexin: a cellular component that links thrombin and plasminogen activator and mediates their binding to cells. Cell. 1980, 21: 37-45. 10.1016/0092-8674(80)90112-9.CrossRefPubMed
25.
Stoller JK, Aboussouan LS: Alpha1-antitrypsin deficiency. Lancet. 2005, 365: 2225-2236. 10.1016/S0140-6736(05)66781-5.CrossRefPubMed
26.
Scott RW, Bergman BL, Bajpai A, Hersh RT, Rodriguez H, Jones BN, Barreda C, Watts S, Baker JB: Protease nexin. Properties and a modified purification procedure. J Biol Chem. 1985, 260: 7029-7034.PubMed
27.
Rothman KJ: No adjustments are needed for multiple comparisons. Epidemiology. 1990, 1: 43-46. 10.1097/00001648-199001000-00010.CrossRefPubMed
Metadata
Title
SERPINE2 haplotype as a risk factor for panlobular type of emphysema
Authors
Mari K Kukkonen
Emmi Tiili
Satu Hämäläinen
Tapio Vehmas
Panu Oksa
Päivi Piirilä
Ari Hirvonen
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2011
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-12-157

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