Search for molecular markers in patients with familial hypercholesterolemia in Chuvash population
Abstract. Familial hypercholesterolemia (FH) is one of the most common hereditary diseases. Genetic testing for FH allows make profiling patients depending on the type of enzyme system defect and prescribe personalized therapy for them.Tarasova L.V., Porfiryeva L.A., Dubova A.V., Kucherova N.Yu., Dimitrieva O.V.
The aim: to search for molecular markers of FH in patients from Chuvashia.
Material and methods. In Republican cardiology dispensary of the Ministry of Healthcare of the Chuvash Republic (Cheboksary), a search for mutation variants of genes associated with the development of genetically determined hypercholesterolemias, as well as with other hereditary diseases with similar phenotypic manifestations, was performed in 12 patients with probable and definite FH (according to the criteria of the Dutch Lipid Clinic Scale, DLCNC).
Results. Molecular markers of FH were detected in 33.3% (n = 4) of patients. Mutations of LDLR and PCSK9 genes in a heterozygous state were identified. Variants of nucleotide sequence in LDLR gene (Chr19: 11224317, NM_000527.5: c.T1465A: p.Tyr489Asn); (Chr19:11217240, rs879254652, NM_000527.5:c.695 1G>T); (Chr19:11218138, rs879254708, NM_000527.5:c.C888A:p.Cys296Ter), in PCSK9 gene (Chr1:55523127, rs137852912, NM_174936.4:c.G1120A:p.Asp374Asn) were found in the examined samples.
Conclusion. A genetic study concerning FH aspect was performed in patients of the Chuvash population for the first time. Of 12 patients in the testing group, 4 had confirmed molecular markers of the disease, and 3 had the most common cause of FH (mutations in LDLR gene), which causes 85–90% of cases of this disease. Current study adds to the knowledge about the spectrum of variants causing FH in Russia and allows not only to confirm the diagnosis in the examined person, but also to make a cascade screening of his relatives for the purpose of early diagnosis of the disease.
Keywords
familial hypercholesterolemia
genetic study
low-density lipoprotein receptor gene
proprotein convertase subtilisin kexin type 9 gene
population
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About the Authors
Larisa V. Tarasova, MD, Dr. Sci. (Medicine), head of the Department of hospital therapy, I.N. Ulyanov Chuvash State University, professor of the Department of public health and healthcare, Institute for Advanced Medical Studies of the Ministry of Healthcare of the Chuvash Republic. Address: 428015, Cheboksary, 45 Moskovsky Avenue.E-mail: tlarisagast18@mail.ru
ORCID: https://orcid.org/0000-0003-1496-0689. Scopus ID: 35777248600. eLibrary SPIN: 4125-7935
Liana A. Porfiryeva, MD, postgraduate student of the Department of faculty and hospital therapy, I.N. Ulyanov Chuvash State University, cardiologist at the Department of cardiology No. 4, Republican Cardiology Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova St.
E-mail: krasnova-liana@mail.ru
ORCID: https://orcid.org/0009-0009-0256-9704
Alexandra V. Dubova, MD, PhD (Medicine), associate professor of the Department of hospital therapy, I.N. Ulyanov Chuvash State University, deputy chief physician for medical affairs of Republican Cardiology Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova St.
E-mail: dubova-sasha@mail.ru
ORCID: https://orcid.org/0000-0002-2788-8762. eLibrary SPIN: 7335-0820
Nadezhda Yu. Kucherova, MD, postgraduate student of the Department of hospital therapy, I.N. Ulyanov Chuvash State University, cardiologist at the Counselling Outpatient Clinic, Republican Cardiology Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova St.
E-mail: nadezda_kan@mail.ru
ORCID: https://orcid.org/0000-0002-9500-3719
Olga V. Dimitrieva, MD, PhD (Medicine), associate professor of the Department of hospital therapy, I.N. Ulyanov Chuvash State University, cardiologist at Republican Cardiology Dispensary of the Ministry of Healthcare of the Chuvash Republic. Address: 428020, Cheboksary, 29A F. Gladkova St.
E-mail: salgarii@mail.ru
ORCID: https://orcid.org/0000-0002-7771-6141. eLibrary SPIN: 7570-5680
