Abstract
BackgroundTo 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.MethodsGenetic 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.ResultsSix, 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/interpretationSerum 25OHD, Ca and PTH levels may not be causally associated with the risk of CAD in patients with diabetes.
Highlights
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
After searching in the PhenoScanner, rs780094 was found strongly associated with metabolic traits such as blood glucose, triglycerides, and total cholesterol, which may represent a pleiotropic single nucleotide polymorphisms (SNPs), while the remained SNPs were not related to any traditional risk factor of CAD in patients with diabetes
The effect of serum 25OHD levels on the risk of CAD in patients with diabetes There was no significant association between genetically predicted serum 25OHD levels, based on six SNPs, and the risk of CAD in patients with diabetes in the IVW analysis (odds ratio (OR) = 1.04, 95% confidence interval (CI): 0.58 - 1.87, P = 0.888)
Summary
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. PTH receptors were found in the endothelial cells, the vascular smooth muscle cells and the cardiomyocytes, which indicated that PTH may serve a role in the pathophysiology of CAD [13, 14]. It remains unclear whether serum 25OHD, Ca and PTH levels were causally associated with CAD risk in patients with diabetes
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