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Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study.
Nutr J. 2019 10 28; 18(1):61.NJ

Abstract

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 GRSsynthesis 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.

Authors+Show Affiliations

Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China. wnj486@126.com.Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, China. luyingli2008@126.com.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31660975

Citation

Chen, Chi, et al. "Association of 25-hydroxyvitamin D With Cardiometabolic Risk Factors and Metabolic Syndrome: a Mendelian Randomization Study." Nutrition Journal, vol. 18, no. 1, 2019, p. 61.
Chen C, Chen Y, Weng P, et al. Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study. Nutr J. 2019;18(1):61.
Chen, C., Chen, Y., Weng, P., Xia, F., Li, Q., Zhai, H., Wang, N., & Lu, Y. (2019). Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study. Nutrition Journal, 18(1), 61. https://doi.org/10.1186/s12937-019-0494-7
Chen C, et al. Association of 25-hydroxyvitamin D With Cardiometabolic Risk Factors and Metabolic Syndrome: a Mendelian Randomization Study. Nutr J. 2019 10 28;18(1):61. PubMed PMID: 31660975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of 25-hydroxyvitamin D with cardiometabolic risk factors and metabolic syndrome: a mendelian randomization study. AU - Chen,Chi, AU - Chen,Yi, AU - Weng,Pan, AU - Xia,Fangzhen, AU - Li,Qin, AU - Zhai,Hualing, AU - Wang,Ningjian, AU - Lu,Yingli, Y1 - 2019/10/28/ PY - 2019/06/14/received PY - 2019/10/14/accepted PY - 2019/10/30/entrez PY - 2019/10/30/pubmed PY - 2020/5/5/medline KW - Cardiometabolic risk factors KW - Mendelian randomization analysis KW - Metabolic syndrome KW - Vitamin D SP - 61 EP - 61 JF - Nutrition journal JO - Nutr J VL - 18 IS - 1 N2 - 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 GRSsynthesis 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. SN - 1475-2891 UR - https://www.unboundmedicine.com/medline/citation/31660975/Association_of_25_hydroxyvitamin_D_with_cardiometabolic_risk_factors_and_metabolic_syndrome:_a_mendelian_randomization_study_ L2 - https://nutritionj.biomedcentral.com/articles/10.1186/s12937-019-0494-7 DB - PRIME DP - Unbound Medicine ER -