{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T02:06:43Z","timestamp":1778897203018,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Lipoprotein (a) [Lp(a)] plays a significant role in atherosclerosis and cardiovascular disease (CVD). Genetic regulation of Lp(a) involves variations in the apo(a) LPA gene, as specific polymorphisms like rs10455872 and rs3798220, both linked to higher Lp(a) levels and CVD. CVD remains the leading global cause of death, with high Lp(a) levels increasingly recognized as a significant factor in younger patients with no other CVD risk factors. We aimed to evaluate the association of LPA genetic variations with Lp(a) levels and its effect on cardiovascular risk as there are existing inconsistent findings. Methods: This case\u2013control study included 251 subjects with a median age of 52 years (interquartile range, IQR = 17) and elevated Lp(a) levels. Cases were subjects who experienced early cardiovascular incidents (women &lt; 65, men &lt; 55 years old), and the control group included subjects without such history. Genotyping of LPA gene polymorphisms (rs10455872 and rs3798220) was performed, and demographic data with Lp(a) levels were collected. To evaluate the association between the LPA genotypes and the risk of cardiovascular incidents (CVI), several logistic regression models were performed. The cut-off points for Lp(a) levels were determined using diagnostic test accuracy measures. Results: The rs3798220-C allele was associated with higher Lp(a) levels (288 \u00b1 166 nmol\/L in cases vs. 189 \u00b1 102 nmol\/L in controls, p &lt; 0.001) and myocardial infarction (53% in cases vs. 36% in controls, p = 0.036). Among cases, 28.9% carried the rs3798220-C allele, compared to 18.7% in controls. The rs10455872-G allele was slightly more prevalent in controls (34.15% vs. 29.69%) but without further significant associations. In this study, the cut-off Lp(a) value of 151 nmol\/L, for patients with a positive family history of early CVD, is associated with a higher chance of developing CVI. Conclusions: This study demonstrates an association between the LPA rs3798220-C allele and higher Lp(a) levels, as well as an increased risk of early onset myocardial infarction. However, the obtained association should further be evaluated at a much larger scale.<\/jats:p>","DOI":"10.3390\/diagnostics15040404","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T09:02:42Z","timestamp":1738918962000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of rs3798220 Polymorphism with Cardiovascular Incidents in Individuals with Elevated Lp(a)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2342-4450","authenticated-orcid":false,"given":"Dunja Leskovar","family":"Leme\u0161i\u0107","sequence":"first","affiliation":[{"name":"Division for Metabolic Diseases, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-1920","authenticated-orcid":false,"given":"Livija","family":"\u0160imi\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Division for Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-4554","authenticated-orcid":false,"given":"Lana","family":"Ganoci","sequence":"additional","affiliation":[{"name":"Division for Pharmacogenomics and Therapy Individualization, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Basic and Clinical Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Gelemanovi\u0107","sequence":"additional","affiliation":[{"name":"Mediterranean Institute for Life Sciences (MedILS), University of Split, 21000 Split, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nediljko","family":"\u0160u\u0107ur","sequence":"additional","affiliation":[{"name":"Division for Metabolic Diseases, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4425-6473","authenticated-orcid":false,"given":"Ivan","family":"Pe\u0107in","sequence":"additional","affiliation":[{"name":"Division for Metabolic Diseases, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Internal Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4019","DOI":"10.1093\/eurheartj\/ehae466","article-title":"European Society of Cardiology: The 2023 Atlas of Cardiovascular Disease Statistics","volume":"45","author":"Timmis","year":"2024","journal-title":"Eur. Heart J."},{"key":"ref_2","unstructured":"(2024, November 29). Croatia Health Statistics Yearbook 2018|GHDx. Available online: https:\/\/ghdx.healthdata.org\/record\/croatia-health-statistics-yearbook-2018."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.pathol.2018.11.003","article-title":"Lipoprotein(a) Catabolism: A Case of Multiple Receptors","volume":"51","author":"McCormick","year":"2019","journal-title":"Pathology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1161\/CIRCULATIONAHA.107.715698","article-title":"Extreme Lipoprotein(a) Levels and Risk of Myocardial Infarction in the General Population: The Copenhagen City Heart Study","volume":"117","author":"Kamstrup","year":"2008","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1001\/jama.2009.1063","article-title":"Lipoprotein(a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality","volume":"302","author":"Tipping","year":"2009","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.jacc.2017.11.014","article-title":"NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of Cardiovascular Disease and Aortic Stenosis","volume":"71","author":"Tsimikas","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jacc.2019.10.057","article-title":"Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome","volume":"75","author":"Bittner","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.jacc.2021.12.032","article-title":"Effect of Pelacarsen on Lipoprotein(a) Cholesterol and Corrected Low-Density Lipoprotein Cholesterol","volume":"79","author":"Yeang","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.jacc.2024.05.058","article-title":"The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results","volume":"84","author":"Rosenson","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1056\/NEJMoa2211023","article-title":"Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease","volume":"387","author":"Rosenson","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s11883-020-00886-0","article-title":"Therapeutic Apheresis for Management of Lp(a) Hyperlipoproteinemia","volume":"22","author":"Pokrovsky","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1159\/000151818","article-title":"Genetics of the Lp System","volume":"13","author":"Berg","year":"1963","journal-title":"Hum. Hered."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1161\/01.ATV.16.6.713","article-title":"Apolipoprotein(a) Kringle IV Repeat Number Predicts Risk for Coronary Heart Disease","volume":"16","author":"Kraft","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1056\/NEJMoa0902604","article-title":"Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease","volume":"361","author":"Clarke","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1590\/1678-4685-gmb-2017-0371","article-title":"The Rs10455872-G Allele of the LPA Gene Is Associated with High Lipoprotein(a) Levels and Increased Aortic Valve Calcium in a Mexican Adult Population","volume":"42","author":"Fragoso","year":"2019","journal-title":"Genet. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3233\/HAB-180353","article-title":"Investigation of LPA Sequence Variants Rs6415084, Rs3798220 with Conventional Coronary Artery Disease in Iranian CAD Patients","volume":"27","author":"Rouhani","year":"2019","journal-title":"Hum. Antibodies"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa1109034","article-title":"Genetic Associations with Valvular Calcification and Aortic Stenosis","volume":"368","author":"Thanassoulis","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.atherosclerosis.2019.08.014","article-title":"2019 ESC\/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk","volume":"290","author":"Mach","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/eurheartj\/ehx095","article-title":"2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in Collaboration with the European Society for Vascular Surgery (ESVS): Document Covering Atherosclerotic Disease of Extracranial Carotid and Vertebral, Mesenteric, Renal, Upper and Lower Extremity ArteriesEndorsed by: The European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vasc","volume":"39","author":"Aboyans","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_20","unstructured":"(2024, December 30). R: The R Project for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). Ggplot2, Springer Cham.","DOI":"10.1007\/978-3-319-24277-4"},{"key":"ref_22","unstructured":"Kassambara, A. (2023). \u201cggplot2\u201d Based Publication Ready Plots, R Package Ggpubr Version 0.6.0, R Foundation. CRAN: Contributed Packages."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.18637\/jss.v098.i11","article-title":"Cutpointr: Improved Estimation and Validation of Optimal Cutpoints in r","volume":"98","author":"Thiele","year":"2021","journal-title":"J. Stat. Softw."},{"key":"ref_24","first-page":"345","article-title":"Impact of Aging on Cardiovascular Diseases: From Chronological Observation to Biological Insights: JACC Family Series","volume":"4","author":"Zhao","year":"2024","journal-title":"JACC: Asia"},{"key":"ref_25","first-page":"236","article-title":"Gender Medicine: Effects of Sex and Gender on Cardiovascular Disease Manifestation and Outcomes","volume":"20","author":"Gebhard","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lv, Y., Cao, X., Yu, K., Pu, J., Tang, Z., Wei, N., Wang, J., Liu, F., and Li, S. (2024). Gender Differences in All-Cause and Cardiovascular Mortality among US Adults: From NHANES 2005\u20132018. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1283132"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pechlivanis, S., Mahabadi, A.A., Hoffmann, P., N\u00f6then, M.M., Broecker-Preuss, M., Erbel, R., Moebus, S., Stang, A., and J\u00f6ckel, K.H. (2020). Association between Lipoprotein(a) (Lp(a)) Levels and Lp(a) Genetic Variants with Coronary Artery Calcification. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-01003-3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.cca.2020.07.029","article-title":"Coronary Artery Disease and the Risk-Associated LPA Variants, Rs3798220 and Rs10455872, in Patients with Suspected Familial Hypercholesterolaemia","volume":"510","author":"Page","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1161\/CIRCGENETICS.110.958371","article-title":"Lipoprotein(a) Genetic Variants Associated with Coronary and Peripheral Vascular Disease but Not with Stroke Risk in the Heart Protection Study","volume":"4","author":"Hopewell","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E002862","DOI":"10.1161\/CIRCGEN.119.002862","article-title":"Genome-Wide Association Study of Peripheral Artery Disease","volume":"14","author":"Stiby","year":"2021","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1161\/CIRCGENETICS.111.959601","article-title":"Genetic Variants in the Apolipoprotein(a) Gene and Coronary Heart Disease","volume":"4","author":"Li","year":"2011","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","article-title":"Lipoprotein(a) in Atherosclerotic Cardiovascular Disease and Aortic Stenosis: A European Atherosclerosis Society Consensus Statement","volume":"43","author":"Kronenberg","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.atherosclerosis.2008.07.019","article-title":"Polymorphism in the Apolipoprotein(a) Gene, Plasma Lipoprotein(a), Cardiovascular Disease, and Low-Dose Aspirin Therapy","volume":"203","author":"Chasman","year":"2008","journal-title":"Atherosclerosis"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/4\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:28:50Z","timestamp":1760027330000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/4\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,7]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["diagnostics15040404"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15040404","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,7]]}}}