Surfactant protein D multimerization and gene polymorphism in COPD and asthma. Issue 3 (28th September 2017)

• Record Type: Journal Article
• Authors: Fakih, Dalia; Akiki, Zeina; Junker, Kirsten; Medlej‐Hashim, Myrna; Waked, Mirna; Salameh, Pascale; Holmskov, Uffe; Bouharoun‐Tayoun, Hasnaa; Chamat, Soulaima; Sorensen, Grith L.; Jounblat, Rania
• Is Part Of: Respirology. Volume 23:Issue 3(2018)
• Page Start: 298
• Page End: 305
• Publication Date: 2017-09-28
• Subjects: asthma -- chronic obstructive pulmonary disease -- multimerization -- single nucleotide polymorphism -- surfactant protein D; Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Periodicals; 612.2
• DOI: 10.1111/resp.13193
• Languages: English
• ISSNs: 1323-7799

Abstract

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. Abstract : We demonstrated for the first time in a Lebanese population cohort that non‐multimerized species of serum surfactant protein D (SP‐D) were dominant in Met11/Met11 COPD and asthmatic patients suggesting that degradation of SP‐D takes place to a significant degree in pulmonary diseases.