Mannose-binding lectin gene polymorphism predicts hospital admissions for COPD infections

Abstract

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 ¼ 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.

Mannose binding lectin (MBL) gene polymorphism and relationship between serum MBL concentrations in COPD patients

“…After analyzing 100, 200, 300 ng/ml, we established a cut off value of 300 ng/ml for MBL deficiency in the present study. In previous literature MBL variants have been reported to be related with low levels of serum MBL [4,33]. We also expected to observe low serum MBL levels for A/B, B/B and D/D genotypes and we determined low (<50 ng/ml) serum MBL concentrations in two individuals having B/B genotype similar to the literature.…”

“…There are some reports demonstrating elevated plasma MBL levels and complement activity in allergic patients although it has not been clarified whether these results are related with genotypic features or disease pathology [27,28]. However, some studies have suggested that genetically reduced MBL levels increase the susceptibility for COPD and asthma [4,29,30], while some others demonstrated the risk of COPD and asthma in MBL deficient patients were not increased [31,32]. Eagan et al, compared 415 COPD patients with 231 controls MBL deficiency was not found more common in COPD patients.…”

“…However, we did not observe any MBL genotype more frequent in COPD patients than the control group, besides MBL deficiency was not found in COPD patients and smokers. Yang et al have studied MBL2 polymorphism and serum MBL2 concentration in a group of COPD patients and smoker controls [4]. A/A genotype frequency was found 73.5%in COPD patients and 73.1%in smoker individuals, whereas A/B genotype frequency was 22.5%, 25.0%and B/B genotype frequency was 4.0%, 1.9%in COPD patients and smoker controls, respectively.…”

“…Genetic variations are the potential risk factors of COPD development and gene polymorphisms which make individuals susceptible to COPD have been under research [3]. Previous reports pointed on the association of functional polymorphisms of mannose binding lectin-2 (MBL) -2 gene with COPD [4,5]. MBL is a member of collectin proteins family [6], whose structure is similar to other best known collectins such as respiratory system surface surfactant proteins A and D [7].…”

Polymorphic variation in surfactant protein B is associated with COPD exacerbations

“…Genetic determinants of COPD exacerbations have not been clearly identified [11,12] despite the observation that COPD exacerbations are more frequent in individuals with prior exacerbations. Variation in exacerbation frequency could relate to different COPD subtypes or to differential susceptibility to infection.…”