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 Vitamin D Life
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 Vitamin D Life
- Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014
- COPD and Vitamin D, concise (46 page) review – Dec 2016
The TOP Vitamin D Binding Protein articles are here:
- Lung Cancer is up to 7 X more deadly if poor vitamin D genes – Oct 2021
- Vitamin D levels in cells, not blood, is important (IVF follicular fluid in this case) – Aug 2021
- Does survival of the less fit mean less health (poor genes may be inherited)
- Topical Vitamin D provides more benefits than oral sometimes - many studies
- Alzheimer’s is associated with all 7 of the genes which restrict vitamin D from getting to tissues – Sept 2018
- Poor Vitamin D response 4X more likely if poor Vitamin D binding proteins - July 2019
- Health problems that run in families are often associated with low vitamin D
- Benefits of Vitamin D often limited by genes
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Vitamin D Binding Protein special Issue – June 2014
- Common Vitamin D gene variants and resulting diseases – Jan 2013
- Vitamin D level can be high, but little benefit: due to kidney, genes, low Magnesium etc.
The Meta-analysis of BREATHING and Vitamin D
- Small doses of Vitamin D do not reduce childhood breathing allergies – meta-analysis Oct 2022
- Asthma treated by Vitamin D - 13th Meta-analysis – July 2022
- COPD treated by Vitamin D – meta-analysis March 2022
- Small amounts of Vitamin D reduce Influenza risk by 22 percent (loading dose is far better) – meta-analysis Jan 2022
- Asthma reduced by Vitamin D, even for those using corticosteroids - meta-analysis 2021
- Small vitamin D doses provide small benefits for acute respiratory infections – Meta-analysis March 2021
- Respiratory Tract Infection risk reduced 2X by Vitamin D loading doses – meta-analysis Jan 2021
- Small vitamin D doses given during pregnancy do not reduce childhood asthma – meta-analysis Dec 2020
- Acute viral respiratory infections (RTI) reduced by Vitamin D - 20 reviews - Aug 2020
- Asthmatics less able to breathe if low vitamin D – meta-analysis Nov 2019
- Asthma is 20 percent more likely with a poor Vitamin D Receptor gene – meta-analysis Oct 2019
- Pneumonia 6X more likely if very low vitamin D – meta-analysis Sept 2019
- Asthma supplementation by Vitamin D (any amount) reduced attacks by 25 percent – meta-analysis April 2019
- Respiratory infections reduced only 20 percent by Vitamin D (ignored dose size, duration, type, etc) – meta-analysis Jan 2019
- Breath better if higher level of Vitamin D – meta-analysis March 2018
- Asthma risk reduced by 67 percent with Vitamin D supplementation if level was initially low– meta-analysis Nov 2017
- Pneumonia patients 3 X more likely to die if low vitamin D – meta-analysis Sept 2017
- Acute respiratory tract infections prevented by vitamin D (even when ignoring the dose size – Meta-analysis Feb 2017
- Asthma exacerbations in children decrease by 60 percent with vitamin D supplementation – meta-analysis – 2015
- Vitamin D during pregnancy reduces risk of childhood asthma by 13 percent – meta-analysis Dec 2016
- Childhood asthma about 1.3 times more likely if poor Vitamin D Receptor – meta-analysis Aug 2016
- COPD 2.8 times more likely to be severe if low vitamin D – meta-analysis Oct 2016
- Lower respiratory tract infections in children associated with Low Vitamin D – meta-analysis May 2016
- Asthma medicines not helped by vitamin D (if only a small amount of D is taken) – meta-analysis Dec 2015
- Asthma not helped by less than 2,000 IU of vitamin D - meta-analysis Aug 2015
- COPD strongly associated with Vitamin D Binding Protein problems – meta-analysis Aug 2015
- COPD severity is associated with Vitamin D deficiency – meta-analyses 2015, 2019
- Infant wheezing 40 percent less likely if mother supplemented with vitamin D, vitamin E, or Zinc – meta-analysis Aug 2015
- Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014
- Asthma reduced 60 percent with vitamin D supplementation – meta-analysis 2014, 2015
- Acute Lower Respiratory Infections in Children - associated with low vitamin D – meta-analysis Dec 2014
- Asthma is strongly associated with low vitamin D (but not COPD) – meta-analysis Feb 2014
- Vitamin D and Respiratory Tract Infections – meta-analysis with charts June 2013
- Vitamin D reduces respiratory tract infections by 40 percent– meta-analysis Dec 2012
- Acute respiratory infection treated by vitamin D in 6 of 12 clinical trials – review Nov 2012
Studies in categories of Intervention AND Breathing
- Chronic tonsillitis virtually eliminated in children by Vitamin D (50,000 IU weekly) – RCT May 2023
- Resulting childhood Asthma cut in half if 4,400 IU Vitamin D (5 ways to improve it) - RCT April 2023
- Several smoking problems treated by Vitamin D (bi-weekly, 50,000 IU) - RCT Dec 2021
- Infant Respiratory Infections not reduced by mothers taking small amount of vitamin D (28,000 weekly)– RCT July 2021
- Asthma and COPD in a few seniors greatly decreased by monthly 100,000 IU Vitamin D – RCT Feb 2021
- Colds substantially reduced by Vitamin D or UV during military training – Jan 2021
- Acute respiratory tract infections not reduced by Vitamin D if already have a good level – Jan 2021
- Upper Respiratory Tract Infections in adults reduced by just 400 IU of vitamin D – RCT Dec 2020
- Those with Asthma or COPD had half the response to Vitamin D – March 2020
- Lower Respiratory Tract Infection in Infants reduced 5.9 X by daily 600 IU of vitamin D (China) - March 2020
- Hay Fever treated by Vitamin D (50,000 IU weekly) – RCT July 2019
- COPD trial to use 80,000 IU of vitamin D weekly – RCT 2021
- Allergic Rhinitis in infants treated by 1,000 IU vitamin D daily – June 2019
- Childhood colds reduced 25 percent by weekly Vitamin D – RCT Jan 2019
- All asthma problems reduced after 1 year of Vitamin D – Nov 2017
- Asthma treated by daily 50,000 IU of Vitamin D – April 2018
- Childhood Respiratory Health hardly improved with 600 IU of vitamin D (need much more) – May 2018
- Allergic rhinitis in children reduced somewhat during pollen season by just 1,000 IU of vitamin D – RCT Jan 2018
- Influenza risk reduced 2X by 2,000 IU of Vitamin D (vs 400), RTI reduced 3X by 400 or more IU – July 2017
- Half the risk of Influenza -A in infants taking 1200 IU of vitamin D for 4 months – RCT Jan 2018
- Risk of infant Asthma cut in half if mother supplemented Vitamin D to get more than 30 ng – RCT Oct 2017
- Childhood asthma problems eliminated for months by 600,000 IU of Vitamin D injection – June 2017
- Reduction of infant asthma may require good vitamin D when lung development starts (4 weeks) – March 2017
- Monthly 100,000 IU of vitamin D decreased respiratory infection but increased falls – Nov 2016
- RTI – Feel much better if increase vitamin D level above 40 ng (4000 IU) – RCT Sept 2015
- Five times less mite allergy when vitamin D added in mid pregnancy and to infant – RCT April 2016
- Childhood asthma still reduced 4 months after 800 IU of Vitamin D daily - RCT Feb 2016
- Asthma exacerbations with colds reduced by 40 percent with vitamin D supplementation – Nov 2015
- Allergic Rhinitis (hay fever) reduced by just 1,000 IU of vitamin D for 30 days – RCT Sept 2015
- Vitamin D loading dose then weekly 50,000 IU not help (COPD) if very deficient – Oct 2015
- Respiratory tract infection eliminated in 36 percent of people by 4000 IU of Vitamin D – RCT Sept 2015
- COPD reduced by 40 percent with monthly 100,000 IU of vitamin D – RCT Jan 2015
- 500,000 IU of vitamin D cut in half the hospital days following a lung failure – RCT 2015
- Respiratory infections (RTI) cut in half by 20,000 IU weekly vitamin D if initially deficient – RCT March 2015
- Wheezing reduced 35 percent if vitamin D added during pregnancy – April 2015
- 5 days of 100,000 IU of Vitamin D increased hemoglobin in critical illness – RCT April 2015
- Respiratory diseases helped by vitamin D if initially have low level – RCT review Jan 2015
- COPD reduced by vitamin D taken once every 60 days – RCT Dec 2014
- Asthma reduced 60 percent with vitamin D supplementation – meta-analysis 2014, 2015
- Respiratory Tract Infection visits 2.5 less likely with vitamin D: Pregnancy 2000 IU, Infant 800 IU – RCT Oct 2014
- Allergy to House dust mite greatly reduced by adding just 600 IU of vitamin D – RCT Nov 2014
- Asthma reduced by weekly 50,000 IU of vitamin D – RCT Aug 2014
- Asthma attacks reduced in half if Vitamin D level higher than 42 nanograms – RCT May 2014
- 2000 IU of vitamin D should improve toddlers health in winter – RCT almost completed Feb 2014
- Bronchial Asthma reduced with 60,000 IU monthly vitamin D – RCT Nov 2013
- COPD fought by Vitamin D - many studies
- Respiratory infections reduced by 63 percent with 4000 IU vitamin D daily - RCT Dec 2012
- Just 300 IU daily of vitamin D reduced respiratory infections by 50% – RCT Aug 2012
- Recurrence of child pneumonia delayed by 100000 IU of vitamin D – RCT Oct 2010
- Sepsis is both prevented and treated by Vitamin D - many studies