Coronary Artery Disease and Serum Calcium Levels: Is There a Genetic Connection?

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Researchers combined the estimates from 6 genetic SNPs to determine the association between calcium and CAD.
Researchers combined the estimates from 6 genetic SNPs to determine the association between calcium and CAD.

Individuals with a genetic predisposition to higher serum calcium levels may have an increased risk for coronary artery disease (CAD) and myocardial infarction (MI), according to an analysis of large-scale genome-wide association studies published in JAMA.

Researchers from the United Kingdom and Sweden used Mendelian randomization to determine whether a causal association existed between genetic variants related to serum calcium levels and risk for CAD and MI. Data were collected from thousands of individuals worldwide from a genome-wide association meta-analysis of serum calcium levels (n=61,079) and from the CAD Genome-wide Replication and Meta-analysis Plus the CAD Genetics (CardiogramplusC4D) consortium's 1000 genomes-based genome-wide association meta-analysis (N=184,305).

The association of a single-nucleotide polymorphism (SNP) with CAD and MI was weighted by its association with calcium. The researchers used an inverse-variance weighted meta-analysis to calculate estimates.

Among the 184,305 individuals included in the Mendelian randomization, there were 60,801 cases of CAD, 70% of which included MI. According to the estimates, the 6 SNPs related to serum calcium explained about 0.8% of the variation in serum calcium levels. When they combined the estimates of the 6 SNPs, the researchers found that the odds ratios per 0.5 mg/dL increase (about 1 standard deviation) in genetically predicted serum calcium levels were 1.25 (95% CI, 1.08-1.45; P =.003) for CAD and 1.24 (95% CI, 1.05-1.46; P =.009) for MI.

"Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown," the researchers wrote.

Study Limitations

  • One specific genetic variant (CASR gene) provided more weight compared with the other variants to the overall estimate of the genetic association between serum calcium levels and CAD.
  • Some overlap between the 2 studies may have occurred, meaning some of the same individuals may have been included in both the genome-wide association meta-analysis and the CardiogramplusC4D's consortium
  • Sex and age data were lacking, as well as a replication data set with a similar large number of CAD cases.

Reference

Larsson SC, Burgess S. Michaӫlsson K. Association of genetic variants related to serum calcium levels with coronary artery disease and myocardial infarction. JAMA. 2017;318(4):371-380. doi:10.1001/jama.2017.8981



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