Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Bækvad-Hansen, Marie; Nordestgaard, Børge G.; Dahl, Morten

doi:10.1183/09031936.00026410

Cited by 22 publications

(17 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reference values for FEV 1 and FVC were internally derived for men and women separately in a subsample of healthy never-smokers using multiple regressions with age and height as covariates [12,18]. If all individuals were used as reference rather than a subsample of never-smokers, the results were similar to those presented.…”

Section: Methodssupporting

confidence: 68%

Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals

et al. 2012

View full text Add to dashboard Cite

Background: MARCO (macrophage receptor with collagenous structure) is a dominant receptor for unopsonized particles and bacteria in the lungs. Reduced function of this receptor due to genetic variation may be associated with susceptibility to chronic obstructive pulmonary disease (COPD) and lung infection. Objectives: To identify novel genetic variants in MARCO that are associated with reduced lung function, or increased risk of COPD or lung infection. Methods: We first screened 760 individuals with extreme lung phenotypes in a large general population study to identify novel variants in the MARCO gene. We next genotyped the entire cohort consisting of 10,604 individuals to assess the clinical relevance of these variants. Results: We identified 4 novel (R124H, K201N, P303L and G340W) and 5 previously described (H101Q, F282S, G319V, K387Q and E511D) non-synonymous variants. When screening the entire cohort for these variants, we found low minor allele frequencies ranging from 0.005 to 5%. None of the individual MARCO genotypes were associated with reduced lung function, or risk of COPD or lung infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95% CI: 1.1–4.4) compared to non-carriers, but none of the other MARCO genotypes were associated with the risk of sepsis. Conclusions: We identified 9 non-synonymous variants in the MARCO gene and showed that these variants are not major risk factors for COPD or lung infection in the Danish population. H101Q heterozygotes had increased sepsis risk, but further research is required to confirm this finding. This study is the first to examine genetic variants in MARCO and the risk of COPD and infections in humans.

show abstract

Section: Methodssupporting

confidence: 68%

Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Pulmonary surfactant-associated proteins (SP) include SP-A, SP-B, SP-C and SP-D which play pivotal roles in the function and metabolism of pulmonary surfactant. SP-B is one of the important SPs and can reduce or alter the surface tension via changing the surface area, which prevents the alveolar collapse (1)(2)(3)(4)(5). Respiratory distress syndrome (RDS) is a multifactorial and multi-gene disease, and a genetic factor has been found to be involved in the pathogenesis of RDS.…”

Section: Introductionmentioning

confidence: 99%

Expression of Pulmonary Surfactant-Associated Protein B in Neonatal Respiratory Distress Syndrome

Yin¹,

Wang²,

Xie³

et al. 2013

Journal of Medical Biochemistry

View full text Add to dashboard Cite

SummaryBackground: The aim of this study was to investigate the role of pulmonary surfactant-associated protein B (SP-B) expression in the pathogenesis of neonatal respiratory distress syndrome (RDS) via detecting the protein and mRNA expression of SP-B. Methods: A total of 60 unrelated neonates who died of RDS were chosen as the RDS group and then subgrouped into ≤32 weeks group, 32∼37 weeks group and ≥37 weeks group (n=20). Sixty neonates who died of other diseases were enrolled as controls and subdivided into 3 matched groups based on the gestational age. Western blot assay and RT-PCR were employed. Results: In the RDS group, SP-B protein expression was reduced or deficient in 8 neonates of which 6 had no SP-B protein expression. In the control group, only 1 had reduced SP-B protein expression. The reduced or deficient SP-B protein expression in 9 neonates of both groups was noted in the ≥37 weeks group. In the RDS group, the SP-B mRNA expression was significantly lower than that in the control group. In the ≤37 weeks group, SP-B mRNA expression was comparable between the RDS group and control group. In the 32∼37 weeks group, the SP-B mRNA expression in the RDS group was significantly reduced when compared with the control group. In the ≥37 weeks group, the SP-B mRNA expression in the RDS group was dramatically lower than that in the control group. Conclusions: Alteration of SP-B expression is present at transcriptional and translational levels. Reduction of SP-B mRNA and protein expression is involved in the pathogenesis of RDS.

show abstract

“…To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. These two cohorts have been successfully used in previous genetic epidemiological studies, where positive associations between variants and disease have been found [16][17][18] and in others where possible associations have been excluded [19][20][21].…”

mentioning

confidence: 99%

2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies

Thomsen¹,

Nordestgaard²,

Sethi³

et al. 2011

European Respiratory Journal

Self Cite

View full text Add to dashboard Cite

The b 2 -adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD).We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism.We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV1) % predicted (trend p50.01) and FEV1/forced vital capacity (FVC) (p50.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV1 % pred and FEV1/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV1 % pred (p50.04) and FEV1/FVC (p,0.001): Thr164Ile homozygotes and heterozygotes had 7% and 1% reduced FEV1 % pred and 6% and 1% reduced FEV1/FVC, respectively, compared with noncarriers. The odds ratios for COPD in Thr164Ile homozygotes and heterozygotes were 4.53 (95% CI 1.54-13.3) and 1.07 (95% CI 0.92-1.25), respectively.Our results suggest that ADRB2 Thr164Ile is associated with reduced lung function and increased risk of COPD in the general population.

show abstract

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

Cited by 22 publications

References 27 publications

Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals

Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals

Expression of Pulmonary Surfactant-Associated Protein B in Neonatal Respiratory Distress Syndrome

2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies

Contact Info

Product

Resources

About