Phenotypical features of heterozygous familial hypercholesterolemia in individuals with LDLR or APOB gene mutations
Abstract
Familial hypercholesterolemia (FHCH) is a hereditary autosomal dominant disease, characterised by lipid metabolism disturbances and high plasma levels of low-density lipoprotein cholesterol (LDL–CH).
Aim. To compare lipid metabolism parameters in patients with various genetic variants of FHCH, and to assess the sensitivity and specificity of biochemical markers for FHCH diagnostics in the relatives of probands.
Material and methods. Lipid metabolism parameters were compared in 123 non-treated patients with genetically confirmed FHCH diagnosis (98 and 5 with LDLR or APOB mutations, respectively) and their healthy relatives without LDLR or APOB mutations.
Results. Similarly to European populations, the Russian population was characterised by higher levels of total CH (TCH) and LDL–CH among patients with LDLR mutations, compared to patients with APOB mutations. In the FHCH diagnostics among relatives, biochemical markers demonstrated high sensitivity (93%) and specificity (82%). Despite lower LDL–CH levels, these diagnostic criteria were also effective in patients with APOB mutations.
Conclusion. In the Russian population, biochemical criteria could be recommended for FHCH diagnostics in the relatives of FHCH probands.
About the Authors
A. N. Meshkov
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
A. I. Ershova
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
N. V. Shcherbakova
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
T. A. Rozhkova
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
M. V. Kalinina
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
V. V. Kukharchuk
Russian Cardiology Scientific and Clinical Complex
Russian Federation
Moscow
Russian Federation
Moscow
S. A. Boytsov
State Research Centre for Preventive Medicine
Russian Federation
Moscow
Russian Federation
Moscow
References
1. Soutar AK, Naoumova RP. Mechanisms of disease: genetic causes of familial hypercholesterolemia. Nat Clin Pract Cardiovasc Med 2007; 4: 214–25.
2. Miserez AR, Keller N. Differences in the phenotypic characteristics of subjects with familial defective apolipoprotein B-100 and familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1995; 15: 1719–29.
3. Fouchier SW, Defesche JC, Kastelein JJ, Sijbrands EJ. Familial defective apolipoprotein B versus familial hypercholesterolemia: an assessment of risk.Semin Vasc Med 2004; 4 (3): 259–64.
4. DeMott K, Nherera L, Shaw EJ, et al. Clinical Guidelines and Evidence Review for Familial hypercholesterolaemia: the identification and management of adults and children with familial hypercholesterolaemia. 2008. London: National Collaborating Centre for Primary Care and Royal College of General Practitioners.
5. Мешков А. Н., Малышев П. П., Кухарчук В. В. Семейная гиперхо-лестеринемия в России: генетическая и фенотипическая характе-ристика. Тер архив 2009; 9: 23–9.
6. Zakharova FM, Damgaard D, Mandelshtam MY, et al. Familial hypercholesterolemia in St.-Petersburg: the known and novel mutations found in the low density lipoprotein receptor gene in Russia. BMC Medical Genetics 2005, 6:6 doi:10.1186/1471–2350–6-6.
7. Lyratzopoulos G, Heller RF, McElduff P, et al. Deprivation and trends in blood pressure, cholesterol, body mass index and smoking among participants of a UK primary care-based cardiovascular risk factor screening programme: both narrowing and widening in cardiovascular risk factor inequalities. Heart 2006; 92: 1198–206.
8. Vlasoff T, Laatikainen T, Korpelainen V, et al. Ten year trends in chronic disease risk factors in the Republic of Karelia, Russia. Eur J Public Health2008; 18 (6): 666–73.
9. Averina M, Nilssen O, Brenn T, et al. High cardiovascular mortality in Russia cannot be explained by the classical risk factors. The Arkhangelsk study 2000. Eur J Epidemiology 2003; 18: 871–8.
10. Ejarque I, Real JT, Martinez-Hervas S, et аl. Evaluation of clinical diagnosis criteria of familial ligand defective apoB 100 and lipoprotein phenotype comparison between LDL receptor gene mutations affecting ligand-binding domain and the R3500Q mutation of the apoB gene in patients from a South European population. Transl Res 2008; 151: 162–7.
11. Marduel M, Carrié A, Sassolas A, et al. Molecular Spectrum of Autosomal Dominant Hypercholesterolemia in France. HUMAN MUTATION Mutation in Brief 31: E1811-E1824 (2010) Online.
Review
For citations:
Meshkov A.N., Ershova A.I., Shcherbakova N.V., Rozhkova T.A., Kalinina M.V., Kukharchuk V.V., Boytsov S.A. Phenotypical features of heterozygous familial hypercholesterolemia in individuals with LDLR or APOB gene mutations. Cardiovascular Therapy and Prevention. 2011;10(8):63-65. (In Russ.)
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