Surfactant protein D multimerization and gene polymorphism in COPD and asthma.
Respirology
; 23(3): 298-305, 2018 03.
Article
de En
| MEDLINE
| ID: mdl-28960651
ABSTRACT
BACKGROUND AND OBJECTIVE:
A structural single nucleotide polymorphism rs721917 in the surfactant protein D (SP-D) gene, known as Met11Thr, was reported to influence the circulating levels and degree of multimerization of SP-D and was associated with both COPD and atopy in asthma. Moreover, disease-related processes are known to degrade multimerized SP-D, however, the degree of the protein degradation in these diseases is not clarified. We aimed to determine the distribution of multimerized (high molecular weight (HMW)) and non-multimerized (low molecular weight (LMW)) species of serum SP-D and their correlation with genetic polymorphisms and presence of disease in Lebanese COPD and asthmatic patients.METHODS:
Serum SP-D levels were measured by ELISA in 88 COPD, 121 asthmatic patients and 223 controls. Randomly selected subjects were chosen for genotyping of rs721917 and multimerization studies. HMW and LMW SP-D were separated by gel permeation chromatography.RESULTS:
Serum SP-D levels were significantly increased in patients with COPD, but not in asthmatic patients, when compared to controls. Met11Thr variation strongly affected serum SP-D levels and the degree of multimerization, but was not associated with COPD and asthma in the study. Remarkably, HMW/LMW serum SP-D ratio was significantly lower in Met11/Met11 COPD and asthmatic patients compared to controls.CONCLUSION:
Collectively, non-multimerized species of serum SP-D were dominant in COPD and asthmatic patients suggesting that degradation of SP-D takes place to a significant degree in pulmonary disease. Assays that can separate SP-D proteolytic breakdown products or modified forms from naturally occurring SP-D trimers may result in optimal disease markers for pulmonary inflammatory diseases.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Asthme
/
ADN
/
Polymorphisme de nucléotide simple
/
Broncho-pneumopathie chronique obstructive
/
Protéine D associée au surfactant pulmonaire
/
Multimérisation de protéines
Limites:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Respirology
Année:
2018
Type de document:
Article
Pays d'affiliation:
Danemark