Analysis of Clinical and Biochemical Characteristics of Patients With Genetically Confirmed Familial Hypercholesterolemia in Russian North Western District Residents.

Aim      To compare results of clinical, laboratory, and genetic examination of patients with familial hypercholesterolemia (FHC).Material and methods  112 patients aged 40.2±17.9 years (49 men) were examined. The gene of low-density lipoprotein receptor (LDLR) was analyzed and evaluated using the Dutch Lipid Clinic Network (DLCN) criterion of lipid score ≥6. The LDLR gene mutation was searched for using the conformational polymorphism analysis followed by sequencing of the DNA of isolated LDLR gene exons.Results Mean variables of the blood lipid profile were total cholesterol (C), 10.12±2.32 mmol/l, LDL-C, 7.72±2.3 mmol/l. Corneal arcus was observed in 15 % of patients, tendon xanthomas in 31.8 %, and xanthelasma palpebrarum in 5.3 %. The types of LDLR gene mutations included missense mutations (42.8 %), mutations causing a premature termination of protein synthesis (41.1 %), and frameshift mutations (16.1 %). In the presence of a mutation in exon 4, patients with IHD compared to patients with no IHD had significantly higher levels of total C (10.88±2.08 mmol/l vs. 8.74±1.57 mmol/l, respectively, р=0.001) and LDL-C (8.60±2.14 mmol/l vs. 6.62±1.79 mmol/l, respectively, р=0.005). Patients with IHD compared to patients with no IHD and a mutation in LDLR gene exon 9 had only a higher LDL-C level (8.96±1.53 mmol/l vs. 6.92±1.59 mmol/l, respectively, р=0.022). A differentiated comparison of IHD patients using a logistic regression depending on the identified type of LDLR gene mutation produced formulas for calculating the odds ratio of IHD and myocardial infarction (MI) with adjustments for the patient's age and baseline LDL.Conclusion      The detection rate of the LDLR gene mutations was 42.8 % for missense mutations, 41.1 % for mutations causing a premature termination of protein synthesis, and 16.1 % for frameshift mutations. Blood lipid profiles did not differ between patients from different cities and with different types of LDLR gene mutations. Blood lipid profiles were different in IHD patients depending on the mutation type.