Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease

Rojo, Paula González; Ramírez, Cristina Pérez; Gálvez-Navas, José María; Pineda-Lancheros, Laura Elena; Rojo-Tolosa, Susana; Ramírez-Tortosa, María Carmen; Morales, Alberto Jiménez

doi:10.3390/ijms23158686

Cited by 12 publications

(7 citation statements)

References 64 publications

(80 reference statements)

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“…The 1,25(OH)2D, is a secosteroid hormone which acts as a ligand by selectively binding to the VDR receptor, a transcription factor which binds to DNA sites called vitamin D response elements (VDREs). There are thousands of VDREs regulating hundreds of genes specifically for each cell [ 10 , 11 , 12 , 13 , 14 ]. In this conceptual framework, vitamin D plays an important role in the inflammatory response and the development of the Th2 phenotype, typical of asthmatic disease.…”

Section: Introductionmentioning

confidence: 99%

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

et al. 2023

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Asthma is a chronic non-communicable disease that affects all age groups. The main challenge this condition poses is its heterogeneity. The role of vitamin D in asthma has aroused great interest, correlating low vitamin D levels and polymorphisms in the genes involved in its metabolic pathway with the risk of asthma. The aim of this study was to evaluate the influence of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolism on the susceptibility to asthma. An observational case-control study was performed, including 221 patients with asthma and 442 controls of Caucasian origin from southern Spain. The SNPs CYP24A1 (rs6068816, rs4809957), CYP27B1 (rs10877012, rs4646536, rs703842, rs3782130), GC (rs7041), CYP2R1 (rs10741657) and VDR (ApaI, BsmI, FokI, Cdx2, TaqI) were analyzed by real-time PCR, using TaqMan probes. The logistic regression model adjusted for body mass index revealed that in the genotype model, carriers of the Cdx2 rs11568820-AA genotype were associated with a higher risk of developing asthma (p = 0.005; OR = 2.73; 95% CI = 1.36–5.67; AA vs. GG). This association was maintained in the recessive model (p = 0.004). The haplotype analysis revealed an association between the ACTATGG haplotype and higher risk of asthma for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130 and rs10877012 genetic polymorphisms (p = 0.039). The other SNPs showed no effect on risk of developing asthma. The Cdx2 polymorphism was significantly associated with the susceptibility of asthma and could substantially act as a predictive biomarker of the disease.

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Section: Introductionmentioning

confidence: 99%

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

et al. 2023

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“…The first occurs in the liver at position 25 through the action of the 25-hydroxylase or CYP2R1 enzyme, resulting in calcidiol or 25(OH)D. This is the metabolite that circulates for the longest in the blood and is therefore the one that is measured to determine serum vitamin D levels [ 14 ]. Then, a second hydroxylation takes place in the kidney through the action of the 1-alpha-hydroxylase or CYP27B1 enzyme, producing calcitriol or 1,25(OH)D. The latter is the active form of vitamin D, which binds to the vitamin D receptor (VDR) in the cell membrane [ 17 , 18 , 19 ]. Through this bond it is translocated to the nucleus, where the dimer binds to the nuclear receptor retinoid (RXR), acting as a transcription factor for vitamin D response elements (VDREs) [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review

et al. 2023

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The objective of this systematic review was to provide a compilation of all the literature available on the association between single-nucleotide polymorphisms (SNPs) in the genes involved in the metabolic pathway of vitamin D and overall survival (OS) and progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). This systematic review was conducted in accordance with the PRISMA guidelines. It included all the literature published up to 1 November 2022 and was carried out in four databases (Medline [PubMed], Scopus, Web of Science, and Embase), using the PICO strategy, with relevant keywords related to the objective. The quality of the studies included was evaluated with an assessment tool derived from the Strengthening the Reporting of Genetic Association Studies (STREGA) statement. Six studies were included in this systematic review. Our findings showed that the BsmI (rs1544410), Cdx-2 (rs11568820), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236), rs4646536, rs6068816, rs7041, and rs10741657 SNPs in the genes that play a part in vitamin D synthesis (CYP2R1, CYP27B1), transport (GC), and metabolism (CYP24A1), as well as in the vitamin D receptor (VDR), are associated with OS and/or PFS in patients with NSCLC. The SNPs in VDR have been the most extensively analyzed. This systematic review summed up the available evidence concerning the association between 13 SNPs in the main genes involved in the vitamin D metabolic pathway and prognosis in NSCLC. It revealed that SNPs in the VDR, CYP27B1, CYP24A1, GC, and CYP2R1 genes could have an impact on survival in this disease. These findings suggest the identification of prognostic biomarkers in NSCLC patients. However, evidence remains sparse for each of the polymorphisms examined, so these findings should be treated with caution.

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“…The existence of a causal relationship between vitamin D and HBP is due to the participation of the active isoform of vitamin D (calcitriol, 1,25-dihydroxyvitamin D or 1,25-(OH) 2 D) in regulating the renin–angiotensin–aldosterone system (RAAS) by inhibiting expression of the gene that codes for renin, a key component in controlling blood pressure (BP) [ 6 , 7 , 8 , 9 ]. Moreover, given the ability of vitamin D to regulate the immune system and its anti-inflammatory activity, a deficiency of this vitamin is associated with the triggering of cytokine-mediated inflammatory processes, which lead to endothelial dysfunction and increased stiffness, contributing to raised BP [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…The inactive ones are cholecalciferol and ergocalciferol. The first is synthesized in the dermis through the action of ultraviolet (UV) radiation, especially UVB (290–320 nm), on 7-dehydrocholesterol, while both the first and the second are incorporated through the diet [ 9 , 17 , 18 ]. Both molecules are transported in the blood bound to vitamin D binding protein (VDBP) or GC, which carries them to the liver, where the CYP2R1 or 25-hydroxylase enzyme carries out a hydroxylation at position 25 of the molecule, producing calcidiol or 25(OH)D. This is the metabolite that remains in the blood for longer and is, therefore, the one that is measured when determining serum levels [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway and Their Relationship with High Blood Pressure Risk

Rojo-Tolosa

Márquez-Pete

Gálvez-Navas

et al. 2023

IJMS

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High blood pressure (HBP) is the leading risk factor for cardiovascular disease (CVD) and all-cause mortality worldwide. The progression of the disease leads to structural and/or functional alterations in various organs and increases cardiovascular risk. Currently, there are significant deficiencies in its diagnosis, treatment, and control. Vitamin D is characterized by its functional versatility and its involvement in countless physiological processes. This has led to the association of vitamin D with many chronic diseases, including HBP and CVD, due to its involvement in the regulation of the renin–angiotensin–aldosterone system. The aim of this study was to evaluate the effect of 13 single nucleotide polymorphisms (SNPs) related to the vitamin D metabolic pathway on the risk of developing HBP. An observational case-control study was performed, including 250 patients diagnosed with HBP and 500 controls from the south of Spain (Caucasians). Genetic polymorphisms in CYP27B1 (rs4646536, rs3782130, rs703842, and rs10877012), CYP2R1 rs10741657, GC rs7041, CYP24A1 (rs6068816, and rs4809957), and VDR (BsmI, Cdx2, FokI, ApaI, and TaqI) were analyzed by real-time PCR using TaqMan probes. Logistic regression analysis, adjusted for body mass index (BMI), dyslipidemia, and diabetes, showed that in the genotypic model, carriers of the GC rs7041 TT genotype were associated with a lower risk of developing HBP than the GG genotype (odds ratio (OR) = 0.44, 95% confidence interval (CI): 0.41–0.77, p = 0.005, TT vs. GG). In the dominant model, this association was maintained; carriers of the T allele showed a lower risk of developing HBP than carriers of the GG genotype (OR = 0.69, 95% CI: 0.47–1.03; TT + TG vs. GG, p = 0.010). Finally, in the additive model, consistent with previous models, the T allele was associated with a lower risk of developing HBP than the G allele (OR = 0.65, 95% CI: 0.40–0.87, p = 0.003, T vs. G). Haplotype analysis revealed that GACATG haplotypes for SNPs rs1544410, rs7975232, rs731236, rs4646536, rs703842, and rs10877012 were associated with a marginally significant lower risk of developing HBP (OR = 0.35, 95% CI: 0.12–1.02, p = 0.054). Several studies suggest that GC 7041 is associated with a lower active isoform of the vitamin D binding protein. In conclusion, the rs7041 polymorphism located in the GC gene was significantly associated with a lower risk of developing HBP. This polymorphism could therefore act as a substantial predictive biomarker of the disease.

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Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease

Cited by 12 publications

References 64 publications

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

Association between Single Nucleotide Polymorphisms Related to Vitamin D Metabolism and the Risk of Developing Asthma

Polymorphisms in VDR, CYP27B1, CYP2R1, GC and CYP24A1 Genes as Biomarkers of Survival in Non-Small Cell Lung Cancer: A Systematic Review

Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway and Their Relationship with High Blood Pressure Risk

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