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

Alexandra Maștaleru,Cristina Rusu,Florin Mitu,Andra Oancea,Irina Abdulan,Ioana Mădălina Zota,Elena Cojocaru,Alexandru Dan Costache,Maria Magdalena Leon Constantin,Cristian Gabriel Ciobanu,Mihai Roca,Sabina Alexandra Cojocariu,Roxana Popescu,Lucian Mihai Antoci

doi:10.3390/jpm12030429

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.

Highlights

Mortality from cardiovascular diseases (CVD) is on the rise, reaching approximately19.9 million deaths in 2019, 85% of which are caused by coronary artery disease (CAD) and stroke
Most of the patients with Familial hypercholesterolemia (FH) had multiple comorbidities when compared to the control group, such as atherosclerotic cardiovascular disease (ASCVD, 32.7% vs. 11.8%), heart failure (HF, 19.2% vs. 11.8%), metabolic syndrome (MetS) (40.4% vs. 11.8%), and modified basal glycemia (MBG, 48.1% vs. 17.6%)
The current study demonstrated that the most frequent three or four concomitant associated polymorphisms found in both groups were Methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, Plasminogen activator inhibitor-1 (PAI-1), and Angiotensin I converting enzyme (ACE)

Summary

Introduction

Mortality from cardiovascular diseases (CVD) is on the rise, reaching approximately. 19.9 million deaths in 2019, 85% of which are caused by coronary artery disease (CAD) and stroke. It is estimated that by 2030, mortality from CVD will reach approximately 23 million deaths. Familial hypercholesterolemia (FH) is defined by very high values of LDL cholesterol that determine in time the development of atherosclerosis process in the arteries (especially in the coronaries and proximal aorta), with subsequent high risk for cardiovascular disease. The DLCN score includes the history of premature CVD for the patient and first degree relatives, high values of LDL (≥190 mg/dL) without any lipid lowering treatment (LLT), and physical signs, such as xanthomata or arcus cornealis [3]

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