Systematic Review and Meta-Analysis to Establish the Association of Common Genetic Variations in Vitamin D Binding Protein With Chronic Obstructive Pulmonary Disease.
Front Genet. 2019 May 16;10:413. doi: 10.3389/fgene.2019.00413. eCollection 2019.
Khanna R1, Nandy D1, Senapati S1.
Items in both categories Breathing and Vitamin D Binding Protein are listed here:
- Asthma more closely associated with poor VDBP gene than with poor Vitamin D level – June 2014
- COPD in Asians twice as likely if poor Vitamin D Binding Protein – meta-analysis May 2019
- COPD strongly associated with Vitamin D Binding Protein problems – meta-analysis Aug 2015
- Gene makes COPD 2.6X more likely unless get more vitamin D – meta-analysis Dec 2014
- Vitamin D Binding Protein, And Airflow In COPD - April 2012
- Genetic link found between vitamin D and COPD – June 2010
- How vitamin D helps the lung via vitamin D-binding protein - May 2010
Vitamin D Binding Protein category listing has
Vitamin D Binding Protein (GC) gene can decrease the bio-available Vitamin D that can get to cells,
- GC is not the only such gene - there are 3 others, all invisible to standard Vitamin D tests
- The bio-available calculation does not notice the effect of GC, CYP27B1, CYP24A1, and VDR
- The actual D getting to the cells is a function of measured D and all 4 genes
- There is >2X increase in 8+ health problems if have poor VDBP (GC)
- It appears that VDBP only blocks oral vitamin D, but not Vitamin D from sun, UV, topical or inhaled (tissue activated)
Vitamin D Binding Protein is invisiable to a Blood test
Background: Vitamin-D binding protein (DBP) also known as GC protein, is a major determinant for vitamin- D metabolism and transport. GC1F, GC1S, and GC2 are the three allelic variants (denoted as rs4588 and rs7041) of GC, and known to be associated with chronic obstructive pulmonary disease (COPD). However, contradictory reports and population specific risk attributed by these alleles warranted detailed genetic epidemiology study to establish the association between GC variants and COPD. In this study we performed a meta-analysis and investigated the genetic architecture of GC locus to establish the association and uncover the plausible reason for allelic heterogeneity.
Methods: Published cross-sectional case control studies were screened and meta-analysis was performed between GC variants and COPD outcome. RevMan-v5.3 software was used to perform random and/or fixed models to calculate pooled odds ratio (Meta-OR). Linkage disequilibrium (LD) and haplotypes at GC locus were evaluated using 1000 Genomes genotype data. In silico functional implications of rs4588 and rs7041 was tested using publicly available tools.
Results: GC1F allele and GC1F/1F genotype were found to confer COPD risk in overall meta-analysis. GC1S/1S was found to confer risk only among Europeans. In silico investigation of rs4588 and rs7041 identified strong eQTL effects and potential role in regulation of GC expression. Large differences in allele frequencies, linkage disequilibrium (LD) and haplotypes were identified at GC locus across different populations (Japanese, African, Europeans, and Indians), which may explain the variable association of different GC alleles in different populations.
Conclusion: GC1F and GC1F/1F impose significant genetic risk for COPD, among Asians. Considerable differences in allele frequencies and LD structure in GC locus may impose population specific risk.