In a major Mendelian randomization study of variants in the HMGCR gene, which encodes the protein through which statins exert their effect, two polymorphisms associated with lower LDL-cholesterol were also associated with higher weight, higher waist circumference, higher glucose and higher diabetes risk.
Alleles near HMGCR are associated with a higher risk of type 2 diabetes, similar to the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials.
HMGCR, our positive control, associated with LDL-C, CAD and a glycemic composite (derived from GWAS meta-analysis of four glycemic traits and diabetes).
In this study, variants in PCSK9 had approximately the same effect as variants in HMGCR on the risk of cardiovascular events and diabetes per unit decrease in the LDL cholesterol level.
These analyses suggested that genotypes of few inflammatory genes, a SNP in HMGCR gene, middle age, gender, low HDL and diabetes were very informative variables to predict the risk of AMI.
We evaluated the association of a single nucleotide polymorphism (rs17238540) in the HMGCR gene with lipid-lowering response to statins in a large population-based cohort of patients with diabetes.