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Article: Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control
Title | Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control |
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Authors | |
Keywords | Vitamin D Exome Chip Mendelian randomization Type 2 diabetes Hypertension Secondary prevention Chinese |
Issue Date | 2022 |
Publisher | BioMed Central Ltd. The Journal's web site is located at https://genesandnutrition.biomedcentral.com/ |
Citation | Genes & Nutrition, 2022, v. 17, article no. 1 How to Cite? |
Abstract | Background:
Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown.
Methods:
This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%.
Results:
After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald’s estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]).
Conclusions:
Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control. |
Persistent Identifier | http://hdl.handle.net/10722/310955 |
ISSN | 2023 Impact Factor: 3.3 2023 SCImago Journal Rankings: 0.838 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chan, YH | - |
dc.contributor.author | Schooling, CM | - |
dc.contributor.author | Zhao, JV | - |
dc.contributor.author | Au Yeung, SL | - |
dc.contributor.author | Hai, JJ | - |
dc.contributor.author | Thomas, GN | - |
dc.contributor.author | Cheng, KK | - |
dc.contributor.author | Jiang, CQ | - |
dc.contributor.author | Wong, YK | - |
dc.contributor.author | Au, KW | - |
dc.contributor.author | Tang, CS | - |
dc.contributor.author | Cheung, CYY | - |
dc.contributor.author | Xu, A | - |
dc.contributor.author | Sham, PC | - |
dc.contributor.author | Lam, TH | - |
dc.contributor.author | Lam, KSL | - |
dc.contributor.author | Tse, HF | - |
dc.date.accessioned | 2022-02-25T04:57:20Z | - |
dc.date.available | 2022-02-25T04:57:20Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Genes & Nutrition, 2022, v. 17, article no. 1 | - |
dc.identifier.issn | 1555-8932 | - |
dc.identifier.uri | http://hdl.handle.net/10722/310955 | - |
dc.description.abstract | Background: Vitamin D (Vit-D) promotes vascular repair and its deficiency is closely linked to the development of type 2 diabetes mellitus (T2DM) and hypertension. Whether genetially predicted vitamin D status (serological 25-hydroxyvitamin D [25(OH)D]) confers secondary protection against cardiovascular diseases (CVD) among high-risk hypertensive-diabetic subjects was unknown. Methods: This is a prospective, individual-data, two-sample Mendelian randomization study. We interrogated 12 prior GWAS-detected SNPs of comprehensive Vit-D mechanistic pathways using high-throughput exome chip analyses in a derivation subcohort (n = 1460) and constructed a genetic risk score (GRS) (rs2060793, rs4588, rs7041; F-statistic = 32, P < 0.001) for causal inference of comprehensive CVD hard clinical endpoints in an independent sample of hypertensive subjects (n = 3746) with prevailing co-morbid T2DM (79%) and serological 25(OH)D deficiency [< 20 ng/mL] 45%. Results: After 55.6 ± 28.9 months, 561 (15%) combined CVD events including myocardial infarction, unstable angina, ischemic stroke, congestive heart failure, peripheral vascular disease, and cardiovascular death had occurred. Kaplan-Meier analysis showed that genetically predicted reduced vitamin D status was associated with reduced event-free survival from combined CVD events (log-rank = 13.5, P = 0.001). Multivariate-adjusted per-allele increase in GRS predicted reduced combined CVD events (HR = 0.90 [0.84 to 0.96], P = 0.002). Mendelian randomization indicates that increased Vit-D exposure, leveraged through each 1 ng/mL genetically instrumented rise of serum Vit-D, protects against combined CVD events (Wald’s estimate: OR = 0.86 [95%CI 0.75 to 0.95]), and myocardial infarction (OR = 0.76 [95%CI 0.60 to 0.90]). Furthermore, genetically predicted increase in Vit-D status ameliorates risk of deviation from achieving guideline-directed hypertension control (JNC-8: systolic target < 150 mmHg) (OR = 0.89 [95%CI 0.80 to 0.96]). Conclusions: Genetically predicted increase in Vit-D status [25(OH)D] may confer secondary protection against incident combined CVD events and myocardial infarction in a hypertensive-diabetic population where serological 25(OH)D deficiency is common, through facilitating blood pressure control. | - |
dc.language | eng | - |
dc.publisher | BioMed Central Ltd. The Journal's web site is located at https://genesandnutrition.biomedcentral.com/ | - |
dc.relation.ispartof | Genes & Nutrition | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Vitamin D | - |
dc.subject | Exome Chip | - |
dc.subject | Mendelian randomization | - |
dc.subject | Type 2 diabetes | - |
dc.subject | Hypertension | - |
dc.subject | Secondary prevention | - |
dc.subject | Chinese | - |
dc.title | Mendelian randomization analysis of vitamin D in the secondary prevention of hypertensive-diabetic subjects: role of facilitating blood pressure control | - |
dc.type | Article | - |
dc.identifier.email | Chan, YH: chanwill@hku.hk | - |
dc.identifier.email | Schooling, CM: cms1@hkucc.hku.hk | - |
dc.identifier.email | Zhao, JV: janezhao@hku.hk | - |
dc.identifier.email | Au Yeung, SL: ayslryan@hku.hk | - |
dc.identifier.email | Cheng, KK: chengkk@hkucc.hku.hk | - |
dc.identifier.email | Jiang, CQ: cqjiang@hkucc.hku.hk | - |
dc.identifier.email | Sham, PC: pcsham@hku.hk | - |
dc.identifier.email | Lam, TH: hrmrlth@HKUCC-COM.hku.hk | - |
dc.identifier.email | Lam, KSL: ksllam@hku.hk | - |
dc.identifier.email | Tse, HF: hftse@hkucc.hku.hk | - |
dc.identifier.authority | Chan, YH=rp01313 | - |
dc.identifier.authority | Schooling, CM=rp00504 | - |
dc.identifier.authority | Zhao, JV=rp02336 | - |
dc.identifier.authority | Au Yeung, SL=rp02224 | - |
dc.identifier.authority | Hai, JJ=rp02047 | - |
dc.identifier.authority | Xu, A=rp00485 | - |
dc.identifier.authority | Sham, PC=rp00459 | - |
dc.identifier.authority | Lam, TH=rp00326 | - |
dc.identifier.authority | Lam, KSL=rp00343 | - |
dc.identifier.authority | Tse, HF=rp00428 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1186/s12263-022-00704-z | - |
dc.identifier.pmid | 35093020 | - |
dc.identifier.pmcid | PMC8903706 | - |
dc.identifier.scopus | eid_2-s2.0-85124044085 | - |
dc.identifier.hkuros | 331889 | - |
dc.identifier.volume | 17 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 1 | - |
dc.identifier.epage | article no. 1 | - |
dc.identifier.isi | WOS:000749177500001 | - |
dc.publisher.place | United Kingdom | - |