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COPD strongly associated with Vitamin D Binding Protein problems – meta-analysis Aug 2015

Vitamin D binding protein gene polymorphisms and chronic obstructive pulmonary disease: a meta-analysis

J Thorac Dis. 2015 Aug; 7(8): 1423–1440., doi: 10.3978/j.issn.2072-1439.2015.08.16
Huan Chen, Lei Zhang, Zhiyi He,corresponding author Xiaoning Zhong, Jianquan Zhang, Meihua Li, and Jing Bai
Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
Contributions: (I) Conception and design: H Chen, L Zhang, J Zhang, X Zhong, Z He; (II) Administrative support: Z He; (III) Collection and assembly of data: H Chen, L Zhang; (IV) Data analysis and interpretation: H Chen, L Zhang, J Bai; (V) Manuscript writing: All authors; (VI) Final approval of manuscript: All authors.
Correspondence to: Zhiyi He. Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. Email: moc.361@revir-iyihz.

Background:
A 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.

Methods:
PubMed, 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.

Results:
Eight 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.

Conclusions:
There 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.


Another study with similar conclusion - Sept 2015

The relationship of vitamin D binding protein polymorphisms with blood vitamin D Level in Korean patients with COPD

European Respiratory Journal
Youngmok Park, Young Sam Kim, Se Kyu Kim, Yeon-Mok Oh, Sang Do Lee, Ji Ye Jung, KOLD Study
DOI: 10.1183/13993003.congress-2015.PA1227 Published 1 September 2015

Background: The blood vitamin D level is generally decreased in COPD, and vitamin D binding protein (GC) polymorphisms are associated with development of COPD.

Aims and Objectives: We explored the relationship of GC polymorphisms and plasma vitamin D level in Korean COPD patients.

Methods: The study population consisted of 175 patients with COPD from Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment of age, BMI, lung function, 6 minutes walking distance, smoking status, smoking pack years, SGRQ total score, and emphysema index. Vitamin D deficiency was defined as plasma 25-OH-Vit D3 level of less than 20 ng/mL.

Results: The average plasma 25-OH-Vit D3 level was 17.5 ng/mL. Frequencies of GC1F, GC1S, and GC2 variants were 44.3%, 23.7%, and 32.0%. Frequencies of genotype 1F-1F, 1F-1S, 1F-2, 1S-1S, 1S-2, and 2-2 were 20.0%, 21.1%, 27.4%, 4.6%, 17.1%, and 9.7%. Compared to non-GC2 group, GC2 group showed lower vitamin D level (15.5 vs. 19.9 ng/mL, P=0.002), lower predicted percent of FEV1 (54.4 vs. 61.1%, P=0.013), and lower FEV1/FVC (45.5 vs. 50.9%, P=0.001).
According to multivariate linear regression analysis, plasma 25-OH-Vit D3 level was associated with subjects with GC2 variant (estimated=-4.492, P=0.007), GC1F variant (estimated=3.698, P=0.042), and genotype 1F-1S (estimated=5.565, P=0.008).
Moreover, GC2 variant (OR=4.12, P=0.007) was risk factor for vitamin D deficiency while GC1F variant (OR=0.29, P=0.047) and genotype 1F-1S (OR=0.31, P=0.047) were protective factors.

Conclusion: GC2 variant was risk factor for vitamin D deficiency while GC1F variant and genotype 1F-1S were protective factors in Korean COPD patients.


Another COPD VDBP meta-analysis - Sept 2015: COPD 1.7X more likely in Asians with poor VDBP

Association of vitamin D-binding protein variants with chronic obstructive pulmonary disease: a meta-analysis.
Genet Mol Res. 2015 Sep 9;14(3):10774-85. doi: 10.4238/2015.September.9.16.
Wang YL1, Kong H1, Xie WP1, Wang H2.

  • 1 Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China hongwang at njmu.edu.cn.

 Download the PDF from VitaminDWiki

Gene polymorphism of vitamin D-binding protein (VDBP) correlates with chronic obstructive pulmonary disease (COPD), but the results remain inconclusive. We aimed to explore the association between VDBP gene polymorphism and COPD. We searched MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure for publications addressing the association between VDBP gene polymorphism and COPD. After qualitative evaluation, randomized controlled trials were pooled using either a fixed- or a random-effect model depending upon the degree of heterogeneity.
Eleven studies with 3144 subjects were included. The genotype group-specific component (GC)*1F-1F was significantly associated with COPD in Asians [odds ratio (OR) = 1.73, 95% confidence interval (CI) = 1.07-2.81, P = 0.03], but not in Caucasians (OR = 1.44, 95%CI = 0.57-3.66, P = 0.45). A protective effect of GC*1F-1S was observed in Asians (OR = 0.70, 95%CI = 0.55-0.89, P = 0.003) but not in Caucasians (OR = 0.93, 95%CI = 0.69-1.24, P = 0.61). There was no association of GC*1S-1S, GC*2-1S and GC*1F-2 with COPD. As for alleles, GC*1F was a risk factor, whereas GC*1S was protective against COPD in Asians; GC*2 was not protective. The genotype GC*1F-1F or allele GC*1F was associated with increased susceptibility to COPD in Asians. No protective effect of genotype GC*2-2 against COPD was found. The protective effects of GC*1F-1S and GC*1S were observed in Asians but not in Caucasians. The VDBP gene polymorphism could be a potential marker for screening of COPD.

PMID: 26400306 DOI: 10.4238/2015.September.9.16


Note: VDBP problems are invisible to Vitamin D tests

See also VitaminDWiki

The TOP Vitamin D Binding Protein articles are here:

The Meta-analysis of BREATHING and Vitamin D

Studies in categories of Intervention AND Breathing

Attached files

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