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Genes involved in innate immunity associated with asbestos-related fibrotic changes

OBJECTIVES: To determine whether genetic polymorphisms in several candidate genes related to innate immunity and protease–antiprotease balance modify individual susceptibility to develop asbestos-related fibrotic pleuropulmonary changes. METHODS: Sixteen polymorphisms from nine genes (NLRP3, CARD8,...

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Autores principales: Kukkonen, Mari K, Vehmas, Tapio, Piirilä, Päivi, Hirvonen, Ari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888604/
https://www.ncbi.nlm.nih.gov/pubmed/24142982
http://dx.doi.org/10.1136/oemed-2013-101555
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author Kukkonen, Mari K
Vehmas, Tapio
Piirilä, Päivi
Hirvonen, Ari
author_facet Kukkonen, Mari K
Vehmas, Tapio
Piirilä, Päivi
Hirvonen, Ari
author_sort Kukkonen, Mari K
collection PubMed
description OBJECTIVES: To determine whether genetic polymorphisms in several candidate genes related to innate immunity and protease–antiprotease balance modify individual susceptibility to develop asbestos-related fibrotic pleuropulmonary changes. METHODS: Sixteen polymorphisms from nine genes (NLRP3, CARD8, TNF, TGFB1, GC, MMP1, MMP9, MMP12 and TIMP2) were genotyped from 951 Finnish asbestos-exposed workers. The genotype/haplotype data were compared to signs of fibrosis and pleural thickenings using linear and logistic regression analysis adjusted for potential confounders. RESULTS: A functional polymorphism (Q705K; rs35829419) in the NLRP3 gene was associated with interstitial lung fibrosis (p=0.013), and the TGFB1 rs2241718 SNP with visceral pleural fibrosis (VPF) (p=0.044). In stratified analysis, the carriage of at least one NLRP3 variant allele conferred a 2.5-fold increased risk for pathological interstitial lung fibrosis (OR 2.44, 95% CI 0.97 to 6.14). Conversely, the carriage of at least one TGFB1 rs2241718 variant allele protected against VPF (OR 0.62, 95% CI 0.39 to 0.98). The TIMP2 rs2277698 SNP and a haplotype consisting of the TGFB1 rs1800469 and rs1800470 SNPs were associated with the degree of pleural thickening calcification (p=0.037 and p=0.035), and the CARD8 rs2043211 SNP with the greatest thickness of pleural plaques (p=0.015). CONCLUSIONS: Our results support the hypothesis that the NLRP3 inflammasome is important in the development of fibrotic lung disease by associating the NLRP3 rs35829419 variant allele with increased risk of asbestos-related interstitial lung fibrosis, and the TGFB1 rs2241718 variant allele with decreased risk of asbestos-related VPF. Polymorphisms in CARD8 and TIMP2 are proposed to modify the development and/or calcification of pleural thickenings.
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spelling pubmed-38886042014-01-14 Genes involved in innate immunity associated with asbestos-related fibrotic changes Kukkonen, Mari K Vehmas, Tapio Piirilä, Päivi Hirvonen, Ari Occup Environ Med Workplace OBJECTIVES: To determine whether genetic polymorphisms in several candidate genes related to innate immunity and protease–antiprotease balance modify individual susceptibility to develop asbestos-related fibrotic pleuropulmonary changes. METHODS: Sixteen polymorphisms from nine genes (NLRP3, CARD8, TNF, TGFB1, GC, MMP1, MMP9, MMP12 and TIMP2) were genotyped from 951 Finnish asbestos-exposed workers. The genotype/haplotype data were compared to signs of fibrosis and pleural thickenings using linear and logistic regression analysis adjusted for potential confounders. RESULTS: A functional polymorphism (Q705K; rs35829419) in the NLRP3 gene was associated with interstitial lung fibrosis (p=0.013), and the TGFB1 rs2241718 SNP with visceral pleural fibrosis (VPF) (p=0.044). In stratified analysis, the carriage of at least one NLRP3 variant allele conferred a 2.5-fold increased risk for pathological interstitial lung fibrosis (OR 2.44, 95% CI 0.97 to 6.14). Conversely, the carriage of at least one TGFB1 rs2241718 variant allele protected against VPF (OR 0.62, 95% CI 0.39 to 0.98). The TIMP2 rs2277698 SNP and a haplotype consisting of the TGFB1 rs1800469 and rs1800470 SNPs were associated with the degree of pleural thickening calcification (p=0.037 and p=0.035), and the CARD8 rs2043211 SNP with the greatest thickness of pleural plaques (p=0.015). CONCLUSIONS: Our results support the hypothesis that the NLRP3 inflammasome is important in the development of fibrotic lung disease by associating the NLRP3 rs35829419 variant allele with increased risk of asbestos-related interstitial lung fibrosis, and the TGFB1 rs2241718 variant allele with decreased risk of asbestos-related VPF. Polymorphisms in CARD8 and TIMP2 are proposed to modify the development and/or calcification of pleural thickenings. BMJ Publishing Group 2014-01 2013-10-04 /pmc/articles/PMC3888604/ /pubmed/24142982 http://dx.doi.org/10.1136/oemed-2013-101555 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Workplace
Kukkonen, Mari K
Vehmas, Tapio
Piirilä, Päivi
Hirvonen, Ari
Genes involved in innate immunity associated with asbestos-related fibrotic changes
title Genes involved in innate immunity associated with asbestos-related fibrotic changes
title_full Genes involved in innate immunity associated with asbestos-related fibrotic changes
title_fullStr Genes involved in innate immunity associated with asbestos-related fibrotic changes
title_full_unstemmed Genes involved in innate immunity associated with asbestos-related fibrotic changes
title_short Genes involved in innate immunity associated with asbestos-related fibrotic changes
title_sort genes involved in innate immunity associated with asbestos-related fibrotic changes
topic Workplace
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888604/
https://www.ncbi.nlm.nih.gov/pubmed/24142982
http://dx.doi.org/10.1136/oemed-2013-101555
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