Genetic association between human chitinases and lung function in COPD
Autor: | Per Bakke, Amund Gulsvik, Esteban G. Burchard, Peter D. Paré, Augusto A. Litonjua, Loubna Akhabir, Edwin K. Silverman, Farzian Aminuddin, John V. Fahy, W. H. Anderson, Celeste Eng, Andrew J. Sandford, Dorota Stefanowicz, Michael H. Cho, J.D. Crapo, John E. Connett, N. R. Anthonisen, David A. Lomas, T.H. Beaty, Max A. Seibold |
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Rok vydání: | 2011 |
Předmět: |
Male
Genotype Population Polymorphism Single Nucleotide Article CHI3L1 Pulmonary Disease Chronic Obstructive Forced Expiratory Volume Genetic variation Genetics medicine Humans education Lung Genetics (clinical) Aged Genetic association COPD education.field_of_study biology Chitinases Smoking Case-control study Genetic Variation Middle Aged medicine.disease respiratory tract diseases Phenotype Case-Control Studies Immunology Chitinase Respiratory Physiological Phenomena biology.protein Female Bronchoalveolar Lavage Fluid |
Zdroj: | Human Genetics. 131:1105-1114 |
ISSN: | 1432-1203 0340-6717 |
Popis: | Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD). Polymorphisms in the chitinase genes were selected based on previous associations with respiratory diseases. Polymorphisms that were associated with lung function level or rate of decline in the Lung Health Study (LHS) cohort were analyzed for association with COPD affection status in four other COPD case-control populations. Chitinase activity and protein levels were also related to genotypes. In the caucasian LHS population, the baseline forced expiratory volume in one second (FEV(1)) was significantly different between the AA and GG genotypic groups of the AMCase rs3818822 polymorphism. Subjects with the GG genotype had higher AMCase protein and chitinase activity compared with AA homozygotes. For CHIT1 rs2494303, a significant association was observed between rate of decline in FEV(1) and the different genotypes. In the African American LHS population, CHIT1 rs2494303 and AMCase G339T genotypes were associated with rate of decline in FEV(1). Although a significant effect of chitinase gene alleles was found on lung function level and decline in the LHS, we were unable to replicate the associations with COPD affection status in the other COPD study groups. |
Databáze: | OpenAIRE |
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