Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections.
Infection frequently causes exacerbations of chronic obstructive pulmonary disease (COPD). Mannose-binding lectin (MBL) is a pattern-recognition receptor that assists in clearing microorganisms. Polymorphisms in the MBL2 gene reduce serum MBL levels and are associated with risk of infection. We studied whether the MBL2 codon 54 B allele affected serum MBL levels, admissions for infective exacerbation in COPD and disease susceptibility. Polymorphism frequency was determined by PCR-RFLP in 200 COPD patients and 104 smokers with normal lung function. Serum MBL was measured as mannan-binding activity in a subgroup of 82 stable COPD patients. Frequency of COPD admissions for infective exacerbation was ascertained for a 2-year period. The MBL2 codon 54 B allele reduced serum MBL in COPD patients. In keeping, patients carrying the low MBL-producing B allele had increased risk of admission for infective exacerbation (OR 4.9, P(corrected)=0.011). No association of MBL2 genotype with susceptibility to COPD was detected. In COPD, serum MBL is regulated by polymorphism at codon 54 in its encoding gene. Low MBL-producing genotypes were associated with more frequent admissions to hospital with respiratory infection, suggesting that the MBL2 gene is disease-modifying in COPD. MBL2 genotype should be explored prospectively as a prognostic marker for infection risk in COPD.
Yang
I A
IA
Division of Thoracic Medicine, The Prince Charles Hospital, and Department of Medicine, University of Queensland, Brisbane, Australia. i.yang@soton.ac.uk
Seeney
S L
SL
Wolter
J M
JM
Anders
E M
EM
McCormack
J G
JG
Tunnicliffe
A M
AM
Rabnott
G C
GC
Shaw
J G
JG
Dent
A G
AG
Kim
S T
ST
Zimmerman
P V
PV
Fong
K M
KM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000031:analogs & derivatives* / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000453:epidemiology / Q000235:genetics*
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin