Genetic association between human chitinases and lung function in COPD.

TitleGenetic association between human chitinases and lung function in COPD.
Publication TypeJournal Article
Year of Publication2012
AuthorsAminuddin, F, Akhabir, L, Stefanowicz, D, Paré, PD, Connett, JE, Anthonisen, NR, Fahy, JV, Seibold, MA, Burchard, EG, Eng, C, Gulsvik, A, Bakke, P, Cho, MH, Litonjua, A, Lomas, DA, Anderson, WH, Beaty, TH, Crapo, JD, Silverman, EK, Sandford, AJ
JournalHum Genet
Volume131
Issue7
Pagination1105-14
Date Published2012 Jul
ISSN1432-1203
KeywordsAged, Bronchoalveolar Lavage Fluid, Case-Control Studies, Chitinase, Female, Forced Expiratory Volume, Genetic Variation, Genotype, Humans, Lung, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Respiratory Physiological Phenomena, Smoking
Abstract

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.

DOI10.1007/s00439-011-1127-1
Alternate JournalHum. Genet.
PubMed ID22200767
PubMed Central IDPMC3771523
Grant List5R01HL064068-04 / HL / NHLBI NIH HHS / United States
G0901786 / / Medical Research Council / United Kingdom
K08 HL097029 / HL / NHLBI NIH HHS / United States
N01-HR-46002 / HR / NHLBI NIH HHS / United States
N01HR76101 / HR / NHLBI NIH HHS / United States
N01HR76102 / HR / NHLBI NIH HHS / United States
N01HR76103 / HR / NHLBI NIH HHS / United States
N01HR76104 / HR / NHLBI NIH HHS / United States
N01HR76105 / HR / NHLBI NIH HHS / United States
N01HR76106 / HR / NHLBI NIH HHS / United States
N01HR76107 / HR / NHLBI NIH HHS / United States
N01HR76108 / HR / NHLBI NIH HHS / United States
N01HR76109 / HR / NHLBI NIH HHS / United States
N01HR76110 / HR / NHLBI NIH HHS / United States
N01HR76111 / HR / NHLBI NIH HHS / United States
N01HR76112 / HR / NHLBI NIH HHS / United States
N01HR76113 / HR / NHLBI NIH HHS / United States
N01HR76114 / HR / NHLBI NIH HHS / United States
N01HR76115 / HR / NHLBI NIH HHS / United States
N01HR76116 / HR / NHLBI NIH HHS / United States
N01HR76118 / HR / NHLBI NIH HHS / United States
N01HR76119 / HR / NHLBI NIH HHS / United States
R01 HL089856 / HL / NHLBI NIH HHS / United States
R01 HL089897 / HL / NHLBI NIH HHS / United States
U01 HL089856 / HL / NHLBI NIH HHS / United States
U01 HL089897 / HL / NHLBI NIH HHS / United States