Surfactant protein-B 121ins2 heterozygosity, reduced pulmonary function, and chronic obstructive pulmonary disease in smokers.
BACKGROUND
Hereditary surfactant protein-B deficiency is an autosomal recessive disorder that causes fatal respiratory distress syndrome in newborns. Seventy percent of the cases of hereditary surfactant protein-B deficiency are caused by homozygosity for the 121ins2 mutation in the surfactant protein-B gene. Individuals heterozygous for this mutation have partial absence of surfactant protein-B and could be at risk of lung disease when exposed to additional risk factors for impaired surfactant function such as tobacco smoking.


OBJECTIVE
To test whether individuals heterozygous for the 121ins2 mutation have reduced lung function and increased risk for chronic obstructive pulmonary disease (COPD) among smokers.


METHODS
We genotyped 47,600 individuals from the adult Danish general population and recorded smoking habits, spirometry, and hospital admissions due to COPD. The study and findings are limited to Danes/Europeans.


RESULTS
We identified 85 individuals heterozygous for the 121ins2 mutation. Smoking interacted statistically with the 121ins2 genotype in predicting FEV(1) % predicted (P = 0.006), FVC % predicted (P = 0.02) and FEV(1)/FVC (P = 0.002), indicating that the effect of genotype differ by smoking status. Among smokers, 121ins2 heterozygous individuals had 9% reduced FEV(1)% predicted (P = 0.0008), 6% reduced FVC % predicted (P = 0.01) and 6% reduced FEV(1)/FVC (P = 0.00007), compared with wild-types. Also among smokers, 121ins2 heterozygous individuals had odds ratios of 2.4 (95% CI, 1.2-4.8) for spirometry-defined COPD and 2.2 (1.0-5.1) for hospitalization due to COPD. Among never-smokers, 121ins2 heterozygous individuals did not differ from wild-types in lung function or risk of COPD.


CONCLUSIONS
Surfactant protein-B 121ins2 heterozygosity is associated with reduced lung function and increased risk for COPD among smokers.
Baekvad-Hansen
Marie
M
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark.
Dahl
Morten
M
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume; D006579:Heterozygote; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
D037701:Pulmonary Surfactant-Associated Protein B