Abstract

Familial hypercholesterolaemia (FH) is a rare disease that tends to be diagnosed lately. In Russia, the genetic and phenotypic characteristics of the disease are not well defined. We investigated 102 patients with definite FH. In 52 of these patients (50.9%) genetic analysis was performed, revealing pathogenic mutations of the low density lipoprotein (LDL) receptor gene in 22 patients. We report here five mutations of the LDL receptor gene found in the Karelian FH sample for the first time. The detection rate of mutations in definite FH patients was 42.3%. Two groups of patients with a definite diagnosis of FH according to the Dutch Lipid Clinic Network criteria were compared: the first group had putatively functionally important LDL receptor gene mutations, while in the second group LDL receptor gene mutations were excluded by single-strand conformation polymorphism analysis. Total and LDL cholesterol levels were higher in the group with LDL receptor mutations compared to the mutation-free population. The frequency of mutations in patients with LDL cholesterol > 6.5 mmol/L was more than 3 times higher than that in patients with LDL < 6.5 mmol/L. Total and LDL cholesterol levels and the frequency of coronary heart disease and myocardial infarction were higher in the group with definite FH compared to groups with probable and possible FH. Cholesterol figures in FH patients of different age and sex from the Karelian population were comparable.

Highlights

  • Familial hypercholesterolaemia (FH) is an autosomal codominant disorder characterized by raised concentrations of low density lipoprotein (LDL) cholesterol in blood and an average 3–13 times greater risk of premature atherosclerotic cardiovascular disease, compared with individuals with normal blood concentrations of LDL cholesterol [1,2,3]

  • The aim of this study was to determine the features of FH in Karelia, Russia and to identify the LDL levels associated with mutation of the LDL receptor in patients with FH in Karelia

  • Genetic analysis was performed in 52 patients with definite FH from this group, revealing a mutation in the LDL receptor gene in 22 of them

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Summary

Introduction

Familial hypercholesterolaemia (FH) is an autosomal codominant disorder characterized by raised concentrations of low density lipoprotein (LDL) cholesterol in blood and an average 3–13 times greater risk of premature atherosclerotic cardiovascular disease, compared with individuals with normal blood concentrations of LDL cholesterol [1,2,3]. This disease leads to accelerated development of atherosclerotic lesions in the blood vessels, especially the coronary arteries, and clinical manifestations of ischemic heart disease (IHD) in young people and even children [4]. The aim of this study was to determine the features of FH in Karelia, Russia (genetic peculiarities; changes in lipid parameters in patients with definite FH) and to identify the LDL levels associated with mutation of the LDL receptor in patients with FH in Karelia

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