Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

TY - JOUR

T1 - Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

AU - Bækvad-Hansen, M

AU - Nordestgaard, B G

AU - Dahl, Morten

PY - 2011/4/1

Y1 - 2011/4/1

N2 - The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status. None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC overall or among smokers (p=0.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p=0.17-0.78). Similar results were obtained for hospitalisation due to COPD (p=0.07-0.93); we could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for homozygotes of 1.25-1.57 or larger for all three polymorphisms. In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine. Copyright

AB - The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status. None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV1) % predicted, forced vital capacity (FVC) % pred and FEV1/FVC overall or among smokers (p=0.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p=0.17-0.78). Similar results were obtained for hospitalisation due to COPD (p=0.07-0.93); we could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for homozygotes of 1.25-1.57 or larger for all three polymorphisms. In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine. Copyright

KW - Adult

KW - Aged

KW - Asthma

KW - Female

KW - Forced Expiratory Volume

KW - Genotype

KW - Humans

KW - Lung

KW - Lung Diseases, Interstitial

KW - Male

KW - Middle Aged

KW - Mutation

KW - Pneumonia

KW - Polymorphism, Genetic

KW - Prospective Studies

KW - Pulmonary Disease, Chronic Obstructive

KW - Pulmonary Surfactant-Associated Protein B

KW - Respiratory Function Tests

KW - Risk

U2 - 10.1183/09031936.00026410

DO - 10.1183/09031936.00026410

M3 - Journal article

C2 - 20693256

SN - 0904-1850

VL - 37

SP - 791

EP - 799

JO - Acta tuberculosea Scandinavica

JF - Acta tuberculosea Scandinavica

IS - 4

ER -