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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
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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. |
format | Online Article Text |
id | pubmed-3269992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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