Genetic Polymorphisms in a Familial Hypercholesterolemia Population from North-Eastern Europe

Abstract

(1) Background: Familial hypercholesterolemia (FH) is one of the most prevalent inherited metabolic disorders. The purpose of the study was to investigate the role in cardiovascular disease (CVD) of PAI-1, ACE, ApoB-100, MTHFR A1298C, and C677T. (2) Methods: From a group of 1499 patients, we included 52 patients diagnosed with FH phenotype and 17 patients in a control group. (3) Results: Most of the FH patients had multiple comorbidities compared to the control group, such as atherosclerosis (48.1% vs. 17.6%), atherosclerotic cardiovascular disease (ASCVD 32.7% vs. 11.8%), and metabolic syndrome (MetS, 40.4% vs. 11.8%). In total, 66.7% of the FH patients had PAI-1 4G/5G genotype and MetS. Between 4G/5G and 4G/4G, a statistically significant difference was observed (p = 0.013). FH patients with ApoB R3500Q polymorphism were correlated with ASCVD (p = 0.031). Both MTHFR C677T and A1298C polymorphisms had a significant correlation with gender, alcohol consumption, and smoking status. ACE polymorphism was associated with ATS in FH patients, statistically significant differences being observed between heterozygous and homozygous D genotype (p = 0.036) as well as between heterozygous and homozygous I genotype (p = 0.021). (4) Conclusions: A link between these polymorphisms was demonstrated in the FH group for ATS, ASCVD, and MetS.

Familial Hypercholesterolaemia as a Predisposing Factor for Atherosclerosis

“…There is much evidence proving the existence of an impact of various genetic parameters on the disease phenotype and CVD risk in the FH population. This applies to genetic variants and SNPs in various genes, including those controlling LDL metabolism, oxidative stress, lipoprotein metabolism, renin angiotensin aldosterone system, and other processes [ 16 ]. Khera et al have found that carriers of an identified FH-causing mutation who suffer from severe hypercholesterolemia had an enhanced CVD risk in comparison to severe hypercholesterolemia patients who did not carry the identified mutation.…”