Genetic association between human chitinases and lung function in COPD.
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.
James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, The University of British Columbia, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada.
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F
Aminuddin
L
L
Akhabir
D
D
Stefanowicz
P D
PD
Paré
J E
JE
Connett
N R
NR
Anthonisen
J V
JV
Fahy
M A
MA
Seibold
E G
EG
Burchard
C
C
Eng
A
A
Gulsvik
P
P
Bakke
M H
MH
Cho
A
A
Litonjua
D A
DA
Lomas
W H
WH
Anderson
T H
TH
Beaty
J D
JD
Crapo
E K
EK
Silverman
A J
AJ
Sandford
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D002688:Chitinases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology*; D012143:Respiratory Physiological Phenomena; D012907:Smoking
C499254:CHIA protein, human; D002688:Chitinases