Dataset Information

Relationship of vitamin D binding protein polymorphisms and lung function in Korean chronic obstructive pulmonary disease.

ABSTRACT:

Purpose

Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population.

Materials and methods

The study cohort consisted of 203 COPD patients and 157 control subjects. GC variants were genotyped by the restriction fragment-length polymorphism method. Repeated measures of lung function data were analyzed using a linear mixed model including sex, age, height, and pack-years of smoking to investigate the association of GC genetic factors and lung function.

Results

GC1F variant was most frequently observed in COPD (46.1%) and controls (42.0%). GC1S variant (29.0% vs. 21.4%; p=0.020) and genotype 1S-1S (8.3% vs. 3.4%; p=0.047) were more commonly detected in control than COPD. According to linear mixed model analysis including controls and COPD, subjects with genotype 1S-1S had 0.427 L higher forced expiratory volume in 1 second (FEV₁) than those with other genotypes (p=0.029). However, interaction between the genotype and smoking pack-year was found to be particularly significant among subjects with genotype 1S-1S; FEV₁ decreased by 0.014 L per smoking pack-year (p=0.001).

Conclusion

This study suggested that GC polymorphism might be associated with lung function and risk of COPD in Korean population. GC1S variant and genotype 1S-1S were more frequently observed in control than in COPD. Moreover, GC1S variant was more common in non-decliners than in rapid decliners among COPD.

SUBMITTER: Jung JY

PROVIDER: S-EPMC4108818 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

Relationship of vitamin D binding protein polymorphisms and lung function in Korean chronic obstructive pulmonary disease.

Jung Ji Ye JY Choi Dong Pil DP Won Sungho S Lee Young Y Shin Ju Hye JH Kim Young Sam YS Kim Se Kyu SK Oh Yeon Mok YM Suh Il I Lee Sang-Do SD

Yonsei medical journal 20140901 5

<h4>Purpose</h4>Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population.<h4>Materials and methods</h4>The study cohort consisted of 203 COPD patients and 157 control subjects. GC variants ...[more]

PMID: 25048491

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Project description:BackgroundA number of polymorphisms in vitamin D binding protein (VDBP) (GC) gene have been implicated in risk of chronic obstructive pulmonary disease (COPD), but the results were controversial. GC1F, GC1S, and GC2 are three common variants of the VDBP gene [single nucleotide polymorphisms (SNPs): rs7041 and rs4588], which were reported to be associated with COPD. This study aimed to explore the association between VDBP gene polymorphisms and COPD.MethodsPubMed, EMBASE, Web of Science (Medline) and Chinese National Knowledge Infrastructure (CNKI) were searched for eligible case-control studies. Study quality was evaluated using the Newcastle-ottawa quality assessment scale (NOS). After the most appreciated genetic model was identified, a meta-analysis was performed to test the association between VDBP gene polymorphism and COPD. The pooled odds ratios (ORs) were performed respectively for the most appreciated genetic model, single allele comparison and homozygous gene model analysis. Summary receiver operating characteristic curve (SROC) analyses were applied to evaluate the diagnostic performance of polymorphism of VDBP to COPD.ResultsEight studies containing 2,216 participants were included. The analyses of the most appropriate genetic models offered significant results in recessive model of GC1F/1S group (OR =2.18), co-dominant genetic model in GC1F/2 group (1F-1F vs. 2-2: OR =4.87; 1F-2 vs. 2-2: OR =1.73; 1F-1F vs. 1F-2: OR =2.27). In single allele comparison, significant results were obtained in GC1F vs. GC1S and GC1F vs. GC2, with ORs were 1.47 and 1.77, respectively. In homozygous genes comparison, the OR was 2.51 in GC1F homozygote vs. other genotypes. Subgroup analyses offered the same significant results in Asian population, but not in Caucasian population. The SROC analyses showed the less accurate performance of polymorphism of VDBP to COPD.ConclusionsThere is a close association between COPD and GC gene polymorphisms. The GC1F allele could be a risk factor, the GC1S and GC2 allele may be protective factors in Asian, but not in Caucasians.

Project description:BackgroundIn chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD.MethodsThe study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL.ResultsThe mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level.ConclusionThe GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD.

Project description:Purpose:We aimed to correlate three polymorphisms of the Hedgehog Interacting Protein (HHIP) gene with the three main phenotypes of the chronic obstructive pulmonary disease (frequent exacerbator (FE), asthma/COPD overlap (ACO), and emphysema with hyperinflation). Patients and methods:A cross-sectional study was carried out in the Department of Pulmonology at the Rio de Janeiro State University from February 2015 to July 2018. A total of 81 patients diagnosed with COPD according to the criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) were enrolled. The subjects were divided into three distinct groups according to their phenotypes (FE, ACO and emphysema-hyperinflation). Three polymorphisms of the HHIP gene that are often reported as allegedly involved in the pathogenesis of COPD were analysed: rs1828591, rs13118928, and rs6537296. Real-time PCR - TAQMAN SNP Genotyping Assay was performed. The statistical analysis was carried out with the SPSS program with a multivariate analysis with a 95% confidence interval. Results:An increase in the frequency of the A allele of the rs13118928 HHIP gene polymorphism was observed in the group of subjects with COPD and emphysema-hyperinflation phenotype when compared with those in the FE phenotype (p=0.019) and subjects with ACO (p=0.04). However, the subjects with emphysema-hyperinflation phenotype presented more often the A allele (p=0.04). The genotypic analysis confirmed the difference between the emphysema-hyperinflation and ACO phenotypes, with a higher prevalence of the AA genotype in the emphysema-hyperinflation group (p=0.04). The ACO and FE phenotype subjects showed no difference in these polymorphisms. No difference was found in the frequency of the polymorphisms rs1828591 (p= 0.552) and rs6537296 (p=0.296) in the three phenotypes evaluated. Conclusion:The presence of the A allele in the rs13118928 polymorphism of the HHIP gene may be related to the emphysema-hyperinflation phenotype.

Project description:BackgroundIn advanced chronic obstructive pulmonary disease (COPD), hypercapnia may occur due to severe bronchial obstruction with lung hyperinflation. Non-invasive ventilation (NIV) provides the standard of care intended to achieve physiological PCO2 levels, thereby reducing overall mortality. The present study aimed to evaluate pulmonary function parameters derived from spirometry (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1]), body plethysmography (residual volume [RV], total lung capacity [TLC]), and lung diffusion capacity for carbon monoxide (single-breath method [DCO-SB], alveolar-volume corrected values [DCO-VA]) as predictors of chronic hypercapnia in patients with advanced COPD.MethodsThis monocentric, retrospective observational study included 423 COPD patients. Receiver operating characteristic (ROC) curve analysis and cross-validation were used to assess lung function parameters' diagnostic accuracy for predicting chronic hypercapnia, with the resulting performance expressed as area under the ROC curve (AUROC). We performed univariable and multivariable binary logistic regression analysis to determine if these parameters were independently associated with chronic hypercapnia, with probabilities reported as odds ratios [OR] with 95% confidence intervals [95%CI].ResultsFVC% (AUROC 0.77 [95%CI 0.72-0.81], P < 0.01) and FEV1% (AURIC 0.75 [95%CI 0.70-0.79], P < 0.01) exhibited reasonable accuracy in the prediction of chronic hypercapnia, whereas lung diffusion capacity performed poorly (AUROC 0.64 [95%CI 0.58-0.71] for DCO-SB%, P < 0.01). FVC% (OR 0.95 [95%CI 0.93-0.97], P < 0.01) and FEV1% (OR 0.97 [95%CI 0.94-0.99], P = 0.029) were the only parameters associated independently with chronic hypercapnia in logistic regression analysis. FVC and FEV1 thresholds that best separated hypercapnic from normocapnic subjects reached 56% and 33% of predicted values.ConclusionsRoutinely collected pulmonary function parameters, particularly FVC% and FEV1%, may predict chronic hypercapnia during COPD progression.

Dataset Information

Relationship of vitamin D binding protein polymorphisms and lung function in Korean chronic obstructive pulmonary disease.

Purpose

Materials and methods

Results

Conclusion

Publications

Relationship of vitamin D binding protein polymorphisms and lung function in Korean chronic obstructive pulmonary disease.

Similar Datasets

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