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Calcium, Its Regulatory Hormones, and Their Causal Role on Blood Pressure : A Two-Sample Mendelian Randomization Study

Giontella, Alice LU orcid ; Lotta, Luca A. ; Baras, Aris ; Minuz, Pietro ; Gill, Dipender ; Melander, Olle LU orcid and Fava, Cristiano LU (2022) In The Journal of clinical endocrinology and metabolism 107(11). p.3080-3085
Abstract

CONTEXT: Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear. OBJECTIVE: To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study. METHODS: From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001)... (More)

CONTEXT: Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear. OBJECTIVE: To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study. METHODS: From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses. RESULTS: Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = -0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis. CONCLUSION: Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood pressure, calcium homeostasis, Mendelian randomization
in
The Journal of clinical endocrinology and metabolism
volume
107
issue
11
pages
6 pages
publisher
Oxford University Press
external identifiers
  • pmid:36062972
  • scopus:85142918834
ISSN
1945-7197
DOI
10.1210/clinem/dgac501
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
id
51dc870e-c626-4992-97e8-f55f0e9c590d
date added to LUP
2022-12-23 10:20:49
date last changed
2024-05-28 22:53:35
@article{51dc870e-c626-4992-97e8-f55f0e9c590d,
  abstract     = {{<p>CONTEXT: Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear. OBJECTIVE: To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study. METHODS: From 4 large genome-wide association studies (GWAS) we obtained independent (r2 &lt; 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses. RESULTS: Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = -0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis. CONCLUSION: Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.</p>}},
  author       = {{Giontella, Alice and Lotta, Luca A. and Baras, Aris and Minuz, Pietro and Gill, Dipender and Melander, Olle and Fava, Cristiano}},
  issn         = {{1945-7197}},
  keywords     = {{blood pressure; calcium homeostasis; Mendelian randomization}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{11}},
  pages        = {{3080--3085}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of clinical endocrinology and metabolism}},
  title        = {{Calcium, Its Regulatory Hormones, and Their Causal Role on Blood Pressure : A Two-Sample Mendelian Randomization Study}},
  url          = {{http://dx.doi.org/10.1210/clinem/dgac501}},
  doi          = {{10.1210/clinem/dgac501}},
  volume       = {{107}},
  year         = {{2022}},
}