Supplementary Material for: Influence of the IDOL Gene Variants on LDL-C Levels in Turkısh Patients with Familial Hypercholesterolemia

INTRODUCTION
The inducible degrader of low-density lipoprotein receptor (IDOL), an E3 ubiquitin ligase, was recently identified as a regulator of the LDL receptor (LDLR) pathway. Shortly, IDOL stimulates LDLR degradation through ubiquitination. However, the association of IDOL gene variants with plasma lipid levels is controversial. No previous study in the Turkish population has reported the relationship between variants of the IDOL gene and LDL-C levels. Our study aims to investigate the effects of genetic variants in the human IDOL gene, which may be a therapeutic target in human cholesterol metabolism, on LDL-C levels.
METHODS
We sequenced all coding, critical intronic, and untranslated regions of the IDOL gene in 125 controls (77 women, 48 men) and 125 patients (64 women, 61 men) with definite or probable Familial Hypercholesterolemia (FH) according to the criteria of the Dutch Lipid Clinic Network (DLCN), in whom no pathogenic/likely pathogenic LDLR variants are present.
RESULTS
We identified 12 different IDOL gene variants, including the p.(N342S) and p.(G51S), whose association with LDL-C levels has been investigated, and classified them into common and rare variants. A rare variant p.(G51S) was only detected in patients the patient group. We compared the Minor Allele Frequency (MAF) distribution of common variants between patient and control groups and examined the association of their genotypic distribution with plasma LDL-C levels using genetic models (dominant, recessive, overdominant, codominant). There was no statistically significant difference in the parameters of the patient and control groups (p>0.05).
CONCLUSION
Our findings suggest that the common IDOL variants we identified do not associate with the LDL-C level in the Turkish population. Rare variants, that were not found to be statistically significant in our study, should be emphasized and supported with further research.