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. 2021 Oct 3;20(1):82.
doi: 10.1186/s12937-021-00735-z.

The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study

Songzan Chen #  1 , Fangkun Yang #  2 , Tian Xu  1 , Yao Wang  1 , Kaijie Zhang  1 , Guosheng Fu  3 , Wenbin Zhang  4
Affiliations

The impact of serum 25-hydroxyvitamin D, calcium, and parathyroid hormone levels on the risk of coronary artery disease in patients with diabetes: a Mendelian randomization study

Songzan Chen et al. Nutr J. .

Abstract

Background: To investigate the causal association between serum 25-hydroxyvitamin D (25OHD), calcium (Ca), and parathyroid hormone (PTH) levels and the risk of coronary artery disease (CAD) in patients with diabetes using a Mendelian randomization approach.

Methods: Genetic signatures associated with serum 25OHD, Ca, and PTH levels were extracted from recently published genome-wide association study (GWAS), including 79,366, 39,400, 29,155 individuals, respectively. Genetic association estimates for CAD in patients with diabetes were obtained from a GWAS of 15,666 individuals with diabetes (3,968 CAD cases, 11,696 controls). The inverse-variance-weighted method was employed for the primary analysis, and other robust methods were applied for sensitivity analyses.

Results: Six, seven and five single nucleotide polymorphisms were identified as instrumental variables for serum 25OHD, Ca and PTH levels, respectively. There was no significant association between genetically predicted serum 25OHD levels and the risk of CAD in patients with diabetes (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888). Similarly, genetically predicted serum Ca (OR = 1.83, 95% CI: 0.62 - 5.35, P = 0.273) and PTH levels (OR = 1.27, 95% CI: 0.67 - 2.44, P = 0.464) were not significantly associated with the risk of CAD in patients with diabetes. These findings were robust in sensitivity analyses.

Conclusions/interpretation: Serum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.

Keywords: Causal association; Coronary artery disease; Diabetes; Mendelian randomization; Serum 25-hydroxyvitamin D levels; Serum calcium levels; Serum parathyroid hormone levels.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Conceptual schematic of the three main assumptions that underpins the two-sample Mendelian randomization analysis of the association between serum 25-hydroxyvitamin D, calcium, parathyroid hormone levels and the risk of coronary artery disease in patients with diabetes. IV indicates instrumental variables; S-25OHD, serum 25-hydroxyvitamin D; S-Ca, serum calcium; S-PTH, serum parathyroid hormone; CAD, coronary artery disease
Fig. 2
Fig. 2
Summary Mendelian randomization estimates of the associations between serum 25-hydroxyvitamin D, calcium, parathyroid hormone levels and the risk of coronary artery disease in patients with diabetes. OR indicates odds ratio; CI, confidence interval; IVW, inverse variance-weighted; MR, Mendelian randomization; MR-PRESSO, MR Pleiotropy Residual Sum and Outlier; S-25OHD, serum 25-hydroxyvitamin D; S-Ca, serum calcium; S-PTH, serum parathyroid hormone
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