Scavenger receptor AI/II truncation, lung function and COPD: a large population-based study

TY - JOUR

T1 - Scavenger receptor AI/II truncation, lung function and COPD

T2 - a large population-based study

AU - Thomsen, M

AU - Nordestgaard, B G

AU - Tybjaerg-Hansen, A

AU - Dahl, M

AU - Dahl, Morten

N1 - © 2010 The Association for the Publication of the Journal of Internal Medicine.

PY - 2011/3

Y1 - 2011/3

N2 - Objectives. The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population. Methods. We genotyped 48741 individuals from the adult Danish general population for Arg293X, and recorded lung function and spirometry-defined COPD. Results. Arg293X homozygotes (n=5) and heterozygotes (n=587), compared with noncarriers (n=48149), had a 6% and 1% reduction in predicted percentage of forced vital capacity (FVC % predicted) (P=0.05) and a nonsignificant 7% and 1% reduction in predicted percentage of forced expiratory volume in one second (FEV1% predicted) (P=0.06), respectively. The Arg293X genotype interacted with gender (P=0.004) and α1-antitrypsin MZ heterozygosity (P=0.049), but not with superoxide dismutase-3 E1I1 heterozygosity (P=0.11) in determining FEV1% predicted. Amongst men, FEV1% predicted and FVC % predicted were both reduced by 4% (P=0.0004 and P=0.0003, respectively) in Arg293X heterozygotes compared with noncarriers. Corresponding values were 14% (P=0.03) and 11% (P=0.04) amongst MZ heterozygotes, and 9% (P=0.03) and 8% (P=0.04) amongst E1I1 heterozygotes, compared with noncarriers. Lung function did not differ between Arg293X heterozygotes and noncarriers amongst females or individuals without MZ and E1I1. Arg293X heterozygosity was associated with spirometry-defined COPD amongst men [odds ratio (95% confidence interval): 1.7 (1.1-2.4)], but not with COPD in the whole cohort or in any other subgroup. Conclusions. SRAI/II Arg293X heterozygotes have reduced lung function and increased COPD risk amongst men. They also have reduced lung function amongst individuals heterozygous for the α1-antitrypsin MZ and superoxide dismutase-3 E1I1 genotypes.

AB - Objectives. The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population. Methods. We genotyped 48741 individuals from the adult Danish general population for Arg293X, and recorded lung function and spirometry-defined COPD. Results. Arg293X homozygotes (n=5) and heterozygotes (n=587), compared with noncarriers (n=48149), had a 6% and 1% reduction in predicted percentage of forced vital capacity (FVC % predicted) (P=0.05) and a nonsignificant 7% and 1% reduction in predicted percentage of forced expiratory volume in one second (FEV1% predicted) (P=0.06), respectively. The Arg293X genotype interacted with gender (P=0.004) and α1-antitrypsin MZ heterozygosity (P=0.049), but not with superoxide dismutase-3 E1I1 heterozygosity (P=0.11) in determining FEV1% predicted. Amongst men, FEV1% predicted and FVC % predicted were both reduced by 4% (P=0.0004 and P=0.0003, respectively) in Arg293X heterozygotes compared with noncarriers. Corresponding values were 14% (P=0.03) and 11% (P=0.04) amongst MZ heterozygotes, and 9% (P=0.03) and 8% (P=0.04) amongst E1I1 heterozygotes, compared with noncarriers. Lung function did not differ between Arg293X heterozygotes and noncarriers amongst females or individuals without MZ and E1I1. Arg293X heterozygosity was associated with spirometry-defined COPD amongst men [odds ratio (95% confidence interval): 1.7 (1.1-2.4)], but not with COPD in the whole cohort or in any other subgroup. Conclusions. SRAI/II Arg293X heterozygotes have reduced lung function and increased COPD risk amongst men. They also have reduced lung function amongst individuals heterozygous for the α1-antitrypsin MZ and superoxide dismutase-3 E1I1 genotypes.

KW - Adult

KW - Aged

KW - Cohort Studies

KW - Denmark

KW - Female

KW - Forced Expiratory Volume

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Heterozygote

KW - Humans

KW - Lung

KW - Male

KW - Middle Aged

KW - Pulmonary Disease, Chronic Obstructive

KW - Scavenger Receptors, Class A

KW - Sex Factors

KW - Vital Capacity

U2 - 10.1111/j.1365-2796.2010.02308.x

DO - 10.1111/j.1365-2796.2010.02308.x

M3 - Journal article

C2 - 21077973

SN - 0955-7873

VL - 269

SP - 340

EP - 348

JO - Acta Medica Scandinavica

JF - Acta Medica Scandinavica

IS - 3

ER -