{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T18:56:03Z","timestamp":1769453763197,"version":"3.49.0"},"reference-count":26,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The work was completed within the framework of the State Assignment","award":["FWNR-2025-0006"],"award-info":[{"award-number":["FWNR-2025-0006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of the study was to characterize the prevalence of comorbidities and molecular genetic status in patients with familial hypercholesterolemia (FH) and non-familial hypercholesterolemia (non-FH). This cross-sectional observational study included 323 patients. Assessments comprised personal and family histories, physical examination, fasting lipid profiling, and molecular genetic testing. Patients with FH were not characterized by an increased prevalence of type 2 diabetes mellitus. In contrast, the non-FH group demonstrated a pronounced cardiometabolic comorbidity profile with a high prevalence of recurrent chronic pancreatitis. Patients with probable or definite FH had a higher prevalence of coronary heart disease and peripheral atherosclerosis, whereas myocardial infarction (MI) was common across all studied groups. Among patients with definite and probable FH, pathogenetic variants were identified in 78.2% and 71.4%, respectively, predominantly in the LDLR gene, with one variant in the APOB gene. In the possible FH group, pathogenic variants were identified in 46.7% of cases (LDLR gene in 64.3% and APOB gene in 28.6%). Patients with FH were characterized by a lower prevalence of concomitant cardiometabolic diseases. The high diagnostic yield of genetic testing in the possible FH category (figured Clinic Network score 3\u20135) suggests that expanding indications for molecular genetic testing to include this patient group should be considered.<\/jats:p>","DOI":"10.3390\/ijms27031214","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:14:23Z","timestamp":1769415263000},"page":"1214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comorbidities and Molecular Genetics Status in Familial and Nonfamilial Hypercholesterolemia: A Single-Center Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-2060","authenticated-orcid":false,"given":"Olga","family":"Timoshchenko","sequence":"first","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-1025","authenticated-orcid":false,"given":"Elena","family":"Shakhtshneider","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"},{"name":"Federal Research Center Institute of Cytology and Genetics, SB RAS, 10 Prospekt Ak. Lavrentyeva, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-545X","authenticated-orcid":false,"given":"Dinara","family":"Ivanoshchuk","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"},{"name":"Federal Research Center Institute of Cytology and Genetics, SB RAS, 10 Prospekt Ak. Lavrentyeva, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-7933","authenticated-orcid":false,"given":"Valentina","family":"Zorina","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"},{"name":"Federal Research Center Institute of Cytology and Genetics, SB RAS, 10 Prospekt Ak. Lavrentyeva, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9371-2178","authenticated-orcid":false,"given":"Pavel","family":"Orlov","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"},{"name":"Federal Research Center Institute of Cytology and Genetics, SB RAS, 10 Prospekt Ak. Lavrentyeva, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3999-8501","authenticated-orcid":false,"given":"Sergey","family":"Semaev","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"},{"name":"Federal Research Center Institute of Cytology and Genetics, SB RAS, 10 Prospekt Ak. Lavrentyeva, Novosibirsk 630090, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4936-8362","authenticated-orcid":false,"given":"Yuliya","family":"Ragino","sequence":"additional","affiliation":[{"name":"Institute of Internal and Preventive Medicine\u2014Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), \u2013Branch of ICG SB RAS, 175\/1 Borisa Bogatkova Str., Novosibirsk 630089, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/s11886-021-01565-5","article-title":"Familial Hypercholesterolemia: Global Burden and Approaches","volume":"23","author":"Tokgozoglu","year":"2021","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Toft-Nielsen, F., Emanuelsson, F., and Benn, M. (2022). Familial Hypercholesterolemia Prevalence Among Ethnicities-Systematic Review and Meta-Analysis. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.840797"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15829\/1560-4071-2019-5-7-13","article-title":"Register of patients with familial hypercholesterolemia and patients of very high cardiovascular risk with lipid-lowering therapy underperformance (RENESSANS)","volume":"24","author":"Yezhov","year":"2019","journal-title":"Russ. J. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.15829\/1560-4071-2021-4538","article-title":"Implemented models and perspectives of managing lipid metabolism disorders. Concept of rare lipid disease centers","volume":"26","author":"Alieva","year":"2021","journal-title":"Russ. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.15829\/1560-4071-2021-4489","article-title":"Organization of lipid centers operation in the Russian Federation\u2014New opportunities","volume":"26","author":"Ezhov","year":"2021","journal-title":"Russ. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5471","DOI":"10.15829\/1560-4071-2023-5471","article-title":"Disorders of lipid metabolism. Clinical Guidelines 2023","volume":"28","author":"Ezhov","year":"2023","journal-title":"Russ. J. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ehaf190","DOI":"10.1093\/eurheartj\/ehaf190","article-title":"2025 Focused Update of the 2019 ESC\/EAS Guidelines for the management of dyslipidaemias","volume":"46","author":"Mach","year":"2025","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Timoshchenko, O., Ivanoshchuk, D., Semaev, S., Orlov, P., Zorina, V., and Shakhtshneider, E. (2024). Diagnosis of Familial Hypercholesterolemia in Children and Young Adults. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010314"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shakhtshneider, E.V., Ivanoshchuk, D.E., Makarenkova, K.V., Orlov, P.S., Timoshchenko, O.V., Bazhan, S.S., Nikitin, Y.P., and Voevoda, M.I. (2017). Cascade genetic screening in diagnostics of heterozygous familial hypercholesterolemia: Clinical case. Russ. J. Cardiol., 178\u2013179. (In Russian).","DOI":"10.15829\/1560-4071-2017-6-178-179"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.15829\/1560-4071-2023-5275","article-title":"Possibilities of lipid clinics in identifying patients with familial hypercholesterolemia","volume":"28","author":"Kim","year":"2023","journal-title":"Russ. J. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Blokhina, A.V., Ershova, A.I., Kiseleva, A.V., Sotnikova, E.A., Zharikova, A.A., Zaicenoka, M., Vyatkin, Y.V., Ramensky, V.E., Kutsenko, V.A., and Litinskaya, O.A. (2024). Clinical and biochemical features of atherogenic hyperlipidemias with different genetic basis: A comprehensive comparative study. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0315693"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101109","DOI":"10.1016\/j.cpcardiol.2022.101109","article-title":"Comorbidities with Familial Hypercholesterolemia (FH): A Systematic Review","volume":"48","author":"Vaseghi","year":"2023","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100086","DOI":"10.1016\/j.ijchy.2021.100086","article-title":"Myocardial strain impairment, heterozygous familial hypercholesterolemia and systemic arterial hypertension: Is there a link?","volume":"9","author":"Vitarelli","year":"2021","journal-title":"Int. J. Cardiol. Hypertens."},{"key":"ref_14","first-page":"114","article-title":"Hypertriglyceridemia as a multidisciplinary problem of modern medicine","volume":"9","author":"Tsygankova","year":"2020","journal-title":"Complex Issues Cardiovasc. Dis."},{"key":"ref_15","first-page":"1374","article-title":"Decline in LDL-C control in patients with dyslipidemia treated with PCSK9-inhibitors: The role of obesity in LDL-C target achievement","volume":"19","author":"Formisano","year":"2025","journal-title":"J. Clin. Lipidol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"550","DOI":"10.5551\/jat.64549","article-title":"Validation of the 2022 Clinical Diagnostic Criteria of Familial Hypercholesterolemia in Japan","volume":"31","author":"Tada","year":"2024","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100999","DOI":"10.1016\/j.cpcardiol.2021.100999","article-title":"Familial Hypercholesterolemia (FH) Registry Worldwide: A Systematic Review","volume":"47","author":"Amerizadeh","year":"2022","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0002-9149(93)90155-6","article-title":"Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics","volume":"72","author":"Williams","year":"1993","journal-title":"Am. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.jacl.2016.07.011","article-title":"US physician practices for diagnosing familial hypercholesterolemia: Data from the CASCADE-FH registry","volume":"10","author":"Ahmad","year":"2016","journal-title":"J. Clin. Lipidol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.atherosclerosis.2022.03.012","article-title":"Diagnosis of familial hypercholesterolemia in a large cohort of Italian genotyped hypercholesterolemic patients","volume":"347","author":"Noto","year":"2022","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.atherosclerosis.2018.08.013","article-title":"Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study","volume":"277","author":"Pirillo","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/eurjpc\/zwae331","article-title":"Performance of LDL-C only compared to the Dutch Lipid Clinic Network Score for screening of familial hypercholesterolaemia: The Austrian experience and literature review","volume":"32","author":"Ferch","year":"2025","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"119185","DOI":"10.1016\/j.atherosclerosis.2025.119185","article-title":"Impact of the clinical diagnostic strata of familial hypercholesterolemia on risk stratification among patients with hypercholesterolemia","volume":"404","author":"Tada","year":"2025","journal-title":"Atherosclerosis"},{"key":"ref_24","first-page":"4455","article-title":"Purification of nucleic acids by extraction with phenol:chloroform","volume":"2006","author":"Sambrook","year":"2006","journal-title":"CSH Protoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41586-023-06045-0","article-title":"A genomic mutational constraint map using variation in 76,156 human genomes","volume":"625","author":"Chen","year":"2024","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:20:39Z","timestamp":1769415639000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,25]]},"references-count":26,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031214"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031214","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,25]]}}}