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SERPINE2 haplotype as a risk factor for panlobular type of emphysema

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...

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Autores principales: Kukkonen, Mari K, Tiili, Emmi, Hämäläinen, Satu, Vehmas, Tapio, Oksa, Panu, Piirilä, Päivi, Hirvonen, Ari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269992/
https://www.ncbi.nlm.nih.gov/pubmed/22145704
http://dx.doi.org/10.1186/1471-2350-12-157
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author Kukkonen, Mari K
Tiili, Emmi
Hämäläinen, Satu
Vehmas, Tapio
Oksa, Panu
Piirilä, Päivi
Hirvonen, Ari
author_facet Kukkonen, Mari K
Tiili, Emmi
Hämäläinen, Satu
Vehmas, Tapio
Oksa, Panu
Piirilä, Päivi
Hirvonen, Ari
author_sort Kukkonen, Mari K
collection PubMed
description 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 (FEV(1)), diffusing capacity (DL(CO)), and specific diffusing capacity (DL(CO)/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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spelling pubmed-32699922012-02-02 SERPINE2 haplotype as a risk factor for panlobular type of emphysema Kukkonen, Mari K Tiili, Emmi Hämäläinen, Satu Vehmas, Tapio Oksa, Panu Piirilä, Päivi Hirvonen, Ari BMC Med Genet Case Control Study 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 (FEV(1)), diffusing capacity (DL(CO)), and specific diffusing capacity (DL(CO)/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. BioMed Central 2011-12-07 /pmc/articles/PMC3269992/ /pubmed/22145704 http://dx.doi.org/10.1186/1471-2350-12-157 Text en Copyright ©2011 Kukkonen et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Case Control Study
Kukkonen, Mari K
Tiili, Emmi
Hämäläinen, Satu
Vehmas, Tapio
Oksa, Panu
Piirilä, Päivi
Hirvonen, Ari
SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title_full SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title_fullStr SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title_full_unstemmed SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title_short SERPINE2 haplotype as a risk factor for panlobular type of emphysema
title_sort serpine2 haplotype as a risk factor for panlobular type of emphysema
topic Case Control Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269992/
https://www.ncbi.nlm.nih.gov/pubmed/22145704
http://dx.doi.org/10.1186/1471-2350-12-157
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