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Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study

BACKGROUND: Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D lev...

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Autores principales: Chen, Chi, Chen, Yi, Weng, Pan, Xia, Fangzhen, Li, Qin, Zhai, Hualing, Wang, Ningjian, Lu, Yingli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819483/
https://www.ncbi.nlm.nih.gov/pubmed/31660975
http://dx.doi.org/10.1186/s12937-019-0494-7
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author Chen, Chi
Chen, Yi
Weng, Pan
Xia, Fangzhen
Li, Qin
Zhai, Hualing
Wang, Ningjian
Lu, Yingli
author_facet Chen, Chi
Chen, Yi
Weng, Pan
Xia, Fangzhen
Li, Qin
Zhai, Hualing
Wang, Ningjian
Lu, Yingli
author_sort Chen, Chi
collection PubMed
description BACKGROUND: Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. METHODS: Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. RESULTS: Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRS(synthesis) determined increase of 25(OH) D levels. CONCLUSIONS: We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings.
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spelling pubmed-68194832019-10-31 Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study Chen, Chi Chen, Yi Weng, Pan Xia, Fangzhen Li, Qin Zhai, Hualing Wang, Ningjian Lu, Yingli Nutr J Research BACKGROUND: Low circulating vitamin D levels have been associated with increased risk of metabolic syndrome (MS) and cardiometabolic risk factors in multiple epidemiology studies. However, whether this association is causal is still unclear. We aimed to test whether genetically lowered vitamin D levels were associated with MS and its metabolic traits, using mendelian randomization (MR) methodology. METHODS: Ten thousand six hundred fifty-five participants were enrolled from the SPECT-China study, which was performed in 23 sites in East China during 2014 to 2016. Using four single-nucleotide polymorphisms (SNPs) in the DHCR7, CYP2R1, GC and CYP24A1 genes with known effects on 25(OH) D concentrations, we created a genetic risk score (GRS) as instrumental variable (IV) to estimate the effect of genetically lowered 25(OH) D on MS and cardiometabolic risk factors. MS was defined according to the International Diabetes Federation criteria. RESULTS: Lower measured 25(OH)D levels were associated with MS (OR 0.921, 95% CI 0.888, 0.954) after multivariable adjustment. However, the MR-derived odds ratio of genetically determined 25(OH) D for risk of MS was 0.977 (95% CI 0.966, 1.030). The MR-derived estimates for raised fasting plasma glucose was 0.578 (95% CI 0.321, 0.980) per 10 nmol/L GRS(synthesis) determined increase of 25(OH) D levels. CONCLUSIONS: We found no evidence that genetically determined reduction in 25(OH)D conferred an increased risk of MS and its metabolic traits. However, we created our GRS only on the basis of common variants, which represent limited amount of variance in 25(OH)D. MR studies using rare variants, and large-scale well-designed RCTs about the effect of vitamin D supplementation on MS are warranted to further validate the findings. BioMed Central 2019-10-28 /pmc/articles/PMC6819483/ /pubmed/31660975 http://dx.doi.org/10.1186/s12937-019-0494-7 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Chen, Chi
Chen, Yi
Weng, Pan
Xia, Fangzhen
Li, Qin
Zhai, Hualing
Wang, Ningjian
Lu, Yingli
Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title_full Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title_fullStr Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title_full_unstemmed Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title_short Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
title_sort association of 25-hydroxyvitamin d with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819483/
https://www.ncbi.nlm.nih.gov/pubmed/31660975
http://dx.doi.org/10.1186/s12937-019-0494-7
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