Surfactant protein D multimerization and gene polymorphism in COPD and asthma

Dalia Fakih, Zeina Akiki, Kirsten Junker, Myrna Medlej-Hashim, Mirna Waked, Pascale Salameh, Uffe Holmskov, Hasnaa Bouharoun-Tayoun, Soulaima Chamat, Grith L Sorensen, Rania Jounblat

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftRespirology
Vol/bind23
Udgave nummer3
Sider (fra-til)298-305
ISSN1323-7799
DOI
StatusUdgivet - mar. 2018

Fingeraftryk

Pulmonary Surfactant-Associated Protein D
Chronic Obstructive Pulmonary Disease
Molecular Weight
Lung Diseases
Genetic Polymorphisms

Citer dette

Fakih, D., Akiki, Z., Junker, K., Medlej-Hashim, M., Waked, M., Salameh, P., ... Jounblat, R. (2018). Surfactant protein D multimerization and gene polymorphism in COPD and asthma. Respirology, 23(3), 298-305. https://doi.org/10.1111/resp.13193
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. / Surfactant protein D multimerization and gene polymorphism in COPD and asthma. I: Respirology. 2018 ; Bind 23, Nr. 3. s. 298-305.
@article{6be7f37f066c43a79fad71ddfa44391d,
title = "Surfactant protein D multimerization and gene polymorphism in COPD and asthma",
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.",
keywords = "Journal Article, multimerization, single nucleotide polymorphism, asthma, surfactant protein D, chronic obstructive pulmonary disease, Asthma/genetics, Pulmonary Surfactant-Associated Protein D/blood, Pulmonary Disease, Chronic Obstructive/blood, Enzyme-Linked Immunosorbent Assay, Humans, Middle Aged, Genotype, Male, Protein Multimerization/genetics, DNA/genetics, Young Adult, Adult, Female, Aged, Polymorphism, Single Nucleotide",
author = "Dalia Fakih and Zeina Akiki and Kirsten Junker and Myrna Medlej-Hashim and Mirna Waked and Pascale Salameh and Uffe Holmskov and Hasnaa Bouharoun-Tayoun and Soulaima Chamat and Sorensen, {Grith L} and Rania Jounblat",
note = "{\circledC} 2017 Asian Pacific Society of Respirology.",
year = "2018",
month = "3",
doi = "10.1111/resp.13193",
language = "English",
volume = "23",
pages = "298--305",
journal = "Respirology",
issn = "1323-7799",
publisher = "Wiley-Blackwell",
number = "3",

}

Fakih, D, Akiki, Z, Junker, K, Medlej-Hashim, M, Waked, M, Salameh, P, Holmskov, U, Bouharoun-Tayoun, H, Chamat, S, Sorensen, GL & Jounblat, R 2018, 'Surfactant protein D multimerization and gene polymorphism in COPD and asthma', Respirology, bind 23, nr. 3, s. 298-305. https://doi.org/10.1111/resp.13193

Surfactant protein D multimerization and gene polymorphism in COPD and asthma. / 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.

I: Respirology, Bind 23, Nr. 3, 03.2018, s. 298-305.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Surfactant protein D multimerization and gene polymorphism in COPD and asthma

AU - Fakih, Dalia

AU - Akiki, Zeina

AU - Junker, Kirsten

AU - Medlej-Hashim, Myrna

AU - Waked, Mirna

AU - Salameh, Pascale

AU - Holmskov, Uffe

AU - Bouharoun-Tayoun, Hasnaa

AU - Chamat, Soulaima

AU - Sorensen, Grith L

AU - Jounblat, Rania

N1 - © 2017 Asian Pacific Society of Respirology.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - Journal Article

KW - multimerization

KW - single nucleotide polymorphism

KW - asthma

KW - surfactant protein D

KW - chronic obstructive pulmonary disease

KW - Asthma/genetics

KW - Pulmonary Surfactant-Associated Protein D/blood

KW - Pulmonary Disease, Chronic Obstructive/blood

KW - Enzyme-Linked Immunosorbent Assay

KW - Humans

KW - Middle Aged

KW - Genotype

KW - Male

KW - Protein Multimerization/genetics

KW - DNA/genetics

KW - Young Adult

KW - Adult

KW - Female

KW - Aged

KW - Polymorphism, Single Nucleotide

U2 - 10.1111/resp.13193

DO - 10.1111/resp.13193

M3 - Journal article

VL - 23

SP - 298

EP - 305

JO - Respirology

JF - Respirology

SN - 1323-7799

IS - 3

ER -

Fakih D, Akiki Z, Junker K, Medlej-Hashim M, Waked M, Salameh P et al. Surfactant protein D multimerization and gene polymorphism in COPD and asthma. Respirology. 2018 mar;23(3):298-305. https://doi.org/10.1111/resp.13193