Impact of polymorphism rs7041 and rs4588 of Vitamin D Binding Protein on the extent of coronary artery disease

25-hydroxyvitamin D deficiency represents a widespread social problem but also an emerging risk factor for cardiovascular disease. Genetic variants of the Vitamin D Binding Protein (VDBP), the main transporter of vitamin D in the bloodstream, have been shown to account for a significant variability...

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Bibliographic Details
Published in:Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2017-09, Vol.27 (9), p.775-783
Main Authors: Daffara, V., Verdoia, M., Rolla, R., Nardin, M., Marino, P., Bellomo, G., Carriero, A., De Luca, G.
Format: Article
Language:English
Subjects:
Aged
Atherosclerosis
Biomarkers - blood
Chi-Square Distribution
Coronary Angiography
Coronary Artery Disease - blood
Coronary Artery Disease - diagnostic imaging
Coronary Artery Disease - epidemiology
Coronary Artery Disease - genetics
Coronary Stenosis - blood
Coronary Stenosis - diagnostic imaging
Coronary Stenosis - epidemiology
Coronary Stenosis - genetics
Female
Gene Frequency
Genetic Association Studies
Genetic Markers
Genetic Predisposition to Disease
Heterozygote
Homozygote
Humans
Italy - epidemiology
Logistic Models
Male
Middle Aged
Multivariate Analysis
Mutation
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide
Polymorphisms
Prevalence
Risk Factors
Severity of Illness Index
VDBP
Vitamin D
Vitamin D - analogs & derivatives
Vitamin D - blood
Vitamin D-Binding Protein - genetics
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Summary:25-hydroxyvitamin D deficiency represents a widespread social problem but also an emerging risk factor for cardiovascular disease. Genetic variants of the Vitamin D Binding Protein (VDBP), the main transporter of vitamin D in the bloodstream, have been shown to account for a significant variability in the levels and systemic effects of vitamin D. We investigated whether the single nucleotide polymorphisms, rs7041 and rs4588, of VDBP are associated to the prevalence and extent of coronary artery disease. A consecutive cohort of patients undergoing coronary angiography in a single centre were included. Significant CAD was defined as at least 1 stenosis >50%, severe CAD for as left main and/or three-vessel disease. VDBP genetic status was assessed by polymerase chain reaction and restriction fragment length polymorphism technique. We included 1080 patients, 57% carried the mutated G allele of rs7041, whereas 22% carried the A allele of rs4588. Higher levels of C- reactive protein were observed in the carriers of G allele of rs7041 (p = 0.02), whereas 25-hydroxyvitamin D levels were similar across groups. A higher prevalence of lesions in the left anterior descending artery and a longer lesion length were observed in “A” carriers for rs4588 (p = 0.04 and p = 0.03, respectively). On the contrary, a higher prevalence of bifurcation lesions and chronic occlusions was observed in G carriers (p = 0.002 and p = 0.01 respectively). Both polymorphisms of VDBP did not affect the prevalence of CAD (rs7041: 79.1% TT vs 80.3% TG vs 78.5% GG, p = 0.81; rs4588 = 80.3% CC vs 78.5% AC + AA, p = 0.49) and severe CAD, (rs7041: 31.1% TT % vs 31.3% TG vs 30.6% GG, p = 0.88; rs4588: 32.2% CC vs 29.3% AC + AA, p = 0.31). Results were confirmed at multivariate analysis, for both rs7041 and rs4588. However, when including the levels of 25-hydroxyvitamin D in the multivariate model, we observed that 25(OH)D status and not genetic variants of VDBP were significantly associated with CAD (25-hydroxyvitamin D OR [95% CI] = 0.99 [0.97–1.0], p = 0.05; rs7041 TG: OR [95% CI] = 1.26 [0.73–2.19], p = 0.41; rs7041 GG: OR [95% CI] = 1.25 [0.82–1.91], p = 0.30; rs4588 AC + AA: OR [95% CI] = 0.76 [0.51–1.13], p = 0.18). This study showed in a large cohort of patients undergoing coronary angiography, that the polymorphisms rs7041 and rs4588 of VDBP are not associated with the levels of 25-hydroxyvitamin D nor with the prevalence and extent of CAD. In fact, 25-hydroxyvitamin D levels but not VDBP ge
ISSN:0939-4753
1590-3729
DOI:10.1016/j.numecd.2017.06.002