The prevalence of 3-hydroxy-3- methylglutaryl-CoA reductase (HMGCR) variants in hypercholesterolemia patients with statins in comparison with healthy controls

The study included 186 participants aged 19 to 75 for the rs12916 analysis. Among them, 100 were healthy volunteers serving as the control group, while 86 were hypercholesterolaemic patients constituting the test group. The patients were treated with either simvastatin (67%) or atorvastatin (33%). For the rs17244841 analysis, 192 participants aged 19 to 75 were studied, comprising 100 healthy volunteers as the control group and 92 hypercholesterolaemic patients as the test group. In this group, 72% received simvastatin and 28% were on atorvastatin. TaqMan® Polymerase Chain Reaction (PCR) genotyping assays were employed for the identification of single nucleotide variants (SNVs) rs12916 and rs17244841. The CKM Human SingleStep ELISA® Kit was used to assess CK levels, and to evaluate the likelihood of statin intolerance, a quantitative questionnaire was utilised.

Results: Among the 86 samples analysed from individuals with diagnosed hypercholesterolaemia, 14% exhibited a high risk of statin intolerance, 48% demonstrated moderate risk, and 38% showed low risk based on the rs12916 variant. Similarly, among the 92 hypercholesterolemia samples analysed, 14% showed high risk, 48% moderate risk, and 38% low risk for statin intolerance associated with the rs17244841 variant.

The genotype distribution for HMGCR rs12916 in the test group and for rs17244841 in both the test and control groups did not align with the Hardy-Weinberg equilibrium (HWE) (p<0.05). However, the genotype distribution for HMGCR rs12916 in the control group was consistent with the HWE.

The rs12916 variant was significantly more common in the control group (42%) than in the test group (36%), (Odds ratio (OR)=0.5318; 95% confidence interval (CI)=0.3543 to 0.8081; p=0.0034).

The frequency of rs17244841 was more common in the control group (61%) than in the test group (50%), (OR)=0.7846; 95% CI=0.5093 to 1.204; p=0.2774). No significant association was found between the risk levels (low, moderate, and high) and statin intolerance for the genotype frequencies for rs12916 (OR=0.5318, 95% CI=0.3543 to 0.8081, relative risk (RR)=0.7439, 95% CI=0.6066 to 0.9036, p=0.0034) or for rs17244841 (OR=0.7846, 95% CI=0.5093 to 1.204, RR=0.888, 95% CI=0.7103 to 1.091, p=0.2774) when based on calculated statin intolerance risk (low risk vs. moderate to high risk). Relative risk quantifies the likelihood of statin intolerance in individuals with these genetic variants compared to those without them. Although patients on simvastatin had higher mean CK levels (25041 pg/mL) compared to atorvastatin users (17650 pg/mL), this difference was not statistically significant (p=0.2111). There was no correlation found between the rs12916 variant and statin intolerance or CK levels (p=0.3658), a positive correlation was observed between the rs17244841 variant and both the severity of statin intolerance and elevated CK levels (p=0.2314).