Precision and Personalized Medicine in Dyslipidemia Management: Innovative and Forward-Looking Approaches to Enhance Clinical Outcomes

Vafaeie, Farzane; Miri-Moghaddam, Ebrahim

Volume 32, Issue 3 (Autumn 2025) J Birjand Univ Med Sci. 2025, 32(3): 185-195 | Back to browse issues page

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Vafaeie F, Miri-Moghaddam E. Precision and Personalized Medicine in Dyslipidemia Management: Innovative and Forward-Looking Approaches to Enhance Clinical Outcomes. J Birjand Univ Med Sci. 2025; 32 (3) :185-195
URL: http://journal.bums.ac.ir/article-1-3533-en.html

Precision and Personalized Medicine in Dyslipidemia Management: Innovative and Forward-Looking Approaches to Enhance Clinical Outcomes

Farzane Vafaeie ^*¹

, Ebrahim Miri-Moghaddam²

1- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran & Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran , farzanevafaeie@gmail.com
2- Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran & Department of Molecular Medicine, Faculty of Medicine, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

Abstract: (905 Views)

Precision and personalized medicine have brought a significant transformation in the management of dyslipidemia. This approach, by considering the unique characteristics of each patient, enables targeted treatments, reduces side effects, and improves quality of life. The development and expansion of these approaches can significantly contribute to reducing the burden of cardiovascular diseases and increasing the lifespan and health of the community. Key tools include omics technologies, such as genomics, proteomics, metabolomics, and pharmacogenomics, which help identify genetic variants, protein profiles, and predict drug responses. Big data analytics and artificial intelligence, including machine learning, enhance risk prediction and treatment optimization by analyzing clinical records and integrating genomic, environmental, and social data. Numerous genetic mutations and variants play a role in dyslipidemia; beyond such well-known genes as LDLR, APOB, and PCSK9, multiple loci identified through large-scale genome-wide association studies are involved. By identifying these mutations through genetic testing, physicians can design more targeted therapies, such as selecting the appropriate drug type and optimal dosage, and even utilizing novel treatments, including PCSK9 inhibitors or RNA-based therapies tailored to each patient. Integrating knowledge of genetic, environmental, and lifestyle factors lays the foundation for precision medicine, enabling the design of treatments perfectly tailored to the unique characteristics of every individual.

Keywords: Cardiovascular disease, Dyslipidemia, Genetic variants, Personalized medicine, Precision medicine, Targeted treatment

Full-Text [PDF 553 kb] (558 Downloads)

Type of Study: Review | Subject: Genetics
Received: 2025/06/21 | Accepted: 2025/09/10 | ePublished ahead of print: 2025/09/24 | ePublished: 2026/01/5

References

1. Hodson R. Precision medicine. Nature. 2016;537(7619):S49-S. https://www.nature.com/articles/537S49a [DOI:10.1038/537S49a] [PMID]

2. Gavriilaki E, Brodsky -RA. Complementopathies and precision medicine. J Clin Invest. 2020;130(5):2152-63. https://www.jci.org/articles/view/136094 [DOI:10.1172/JCI136094] [PMID] []

3. Banach M, Surma S, Reiner Z, Katsiki N, Penson PE, Fras Z, et al. Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach.Cardiovasc Diabetol. 2022;21(1):263. https://link.springer.com/article/10.1186/s12933-022-01684-5 [DOI:10.1186/s12933-022-01684-5] [PMID] []

4. Vafaeie F, Farkhondeh T, Samarghandian S, Miri-Moghaddam E. Protective Effect of Curcumin on Metabolic Syndrome Components through the Microbiota. Curr Med Chem. 2025; 32(39). https://www.benthamdirect.com/content/journals/cmc/10.2174/0109298673371503250210092741 DOI:10.2174/0109298673371503250210092741 [DOI:10.2174/0109298673371503250210092741] [PMID]

5. Graça R, Alves AC, Zimon M, Pepperkok R, Bourbon M. Functional profiling of LDLR variants: Important evidence for variant classification: Functional profiling of LDLR variants. J Clin Lipidol. 2022;16(4):516-24. https://www.sciencedirect.com/science/article/pii/S1933287422000757 [DOI:10.1016/j.jacl.2022.04.005] [PMID]

6. Parsamanesh N, Kooshkaki O, Siami H, Santos RD, Jamialahmadi T, Sahebkar A. Gene and cell therapy approaches for familial hypercholesterolemia: An update. Drug Discov Today. 2023;28(3):103470. https://www.sciencedirect.com/science/article/pii/S1359644622004639 https://pubmed.ncbi.nlm.nih.gov/36572377/ [DOI:10.1016/j.drudis.2022.103470] [PMID]

7. Khera AV, Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations.Nat Genet. 2018;50(9):1219-24.https://www.nature.com/articles/s41588-018-0183-z [DOI:10.1038/s41588-018-0183-z] [PMID] []

8. Raal FJ, Stein EA, Dufour R, Turner T, Civeira F, Burgess L, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):331-40.https://www.jvascsurg.org/article/S0741-5214(15)01953-9/fulltext [DOI:10.1016/S0140-6736(14)61399-4] [PMID]

9. McDonagh M, Peterson K, Holzhammer B, Fazio S. A systematic review of PCSK9 inhibitors alirocumab and evolocumab.J Manag Care Spec Pharm. 2016;22(6):641-53q.https://www.jmcp.org/doi/abs/10.18553/jmcp.2016.22.6.641 https://pubmed.ncbi.nlm.nih.gov/27231792/ [DOI:10.18553/jmcp.2016.22.6.641] [PMID] []

10. Arnold N, Koenig W. PCSK9 inhibitor wars: how does inclisiran fit in with current monoclonal antibody inhibitor therapy? Considerations for patient selection.Curr Cardiol Rep. 2022;24(11):1657-67.https://link.springer.com/article/10.1007/s11886-022-01782-6 https://pubmed.ncbi.nlm.nih.gov/36087240/ [DOI:10.1007/s11886-022-01782-6] [PMID] []

11. Surendran RP, Visser ME, Heemelaar S, Wang J, Peter J, Defesche JC, et al. Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. J Intern Med. 2012;272(2):185-96.https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2012.02516.x https://pubmed.ncbi.nlm.nih.gov/22239554/ [DOI:10.1111/j.1365-2796.2012.02516.x] [PMID] []

12. Abedi A, Yildirim Şimşir I, Bayram F, Onay H, Ozgur S, Mcintyre A, et al. Genetic variants associated with severe hypertriglyceridemia: LPL, APOC2, APOA5, GPIHBP1, LMF1, and APOE.Turk Kardiyol Dern Ars. 2023; 51(1): 10-21. https://jag.journalagent.com/tkd/pdfs/TKDA-98544-ORIGINAL_ARTICLE-YILDIRIM_SIMSIR.pdf [DOI:10.5543/tkda.2022.98544] [PMID]

13. Raal FJ, Rosenson RS, Reeskamp LF, Kastelein JJ, Rubba P, Duell PB, et al. The long-term efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia. JACC Adv. 2023;2(9):100648. https://www.jacc.org/doi/abs/10.1016/j.jacadv.2023.100648 https://pubmed.ncbi.nlm.nih.gov/38938723/ [DOI:10.1016/j.jacadv.2023.100648] [PMID] []

14. Wan P, Tang S, Lin D, Lu Y, Long M, Xiao L, et al. Base Editing Gene Therapy for Heterozygous Familial Hypercholesterolemia. medRxiv. 2025:2025.04. 17.25325983. https://www.medrxiv.org/content/10.1101/2025.04.17.25325983.abstract DOI: 10.1101/2025.04.17.25325983 [DOI:10.1101/2025.04.17.25325983]

15. Wilkins JT, Li RC, Sniderman A, Chan C, Lloyd-Jones DM. Discordance between apolipoprotein B and LDL-cholesterol in young adults predicts coronary artery calcification: the CARDIA study. J Am Coll Cardiol. 2016;67(2):193-201. https://www.jacc.org/doi/abs/10.1016/j.jacc.2015.10.055 [DOI:10.1016/j.jacc.2015.10.055] [PMID] []

16. Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen MJ, de Graaf J, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337-45. https://www.ahajournals.org/doi/abs/10.1161/CIRCOUTCOMES.110.959247 [DOI:10.1161/CIRCOUTCOMES.110.959247] [PMID]

17. Seidah NG. PCSK9 as a therapeutic target of dyslipidemia. Expert Opin Ther Targets. 2009;13(1):19-28. https://www.tandfonline.com/doi/abs/10.1517/14728220802600715 [DOI:10.1517/14728220802600715] [PMID]

18. Alves AC, Etxebarria A, Soutar AK, Martin C, Bourbon M. Novel functional APOB mutations outside LDL-binding region causing familial hypercholesterolaemia. Hum Mol Genet. 2014;23(7):1817-28. https://academic.oup.com/hmg/article-abstract/23/7/1817/653825 [DOI:10.1093/hmg/ddt573] [PMID]

19. Warden BA, Duell PB. Inclisiran: a novel agent for lowering apolipoprotein B-containing lipoproteins. J Cardiovasc Pharmacol. 2021;78(2):e157-e74. https://journals.lww.com/cardiovascularpharm/fulltext/2021/08000/Inclisiran__A_Novel_Agent_for_Lowering.1.aspx?context=LatestArticles https://pubmed.ncbi.nlm.nih.gov/33990512/ [DOI:10.1097/FJC.0000000000001053] [PMID]

20. Sahebkar A, Watts GF. New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect?Cardiovasc Drugs Ther. 2013;27(6):559-67. https://link.springer.com/article/10.1007/s10557-013-6479-4 [DOI:10.1007/s10557-013-6479-4] [PMID]

21. Vega R, Garkaviy P, Knöchel J, Barbour A, Rudvik A, Laru J, et al. AZD0780, the first oral small molecule PCSK9 inhibitor for the treatment of hypercholesterolemia: Results from a randomized, single-blind, placebo-controlled phase 1 trial. Atherosclerosis. 2024;395. https://www.atherosclerosis-journal.com/article/S0021-9150(24)01081-5/abstract DOI: 10.1016/j.atherosclerosis.2024.118514 [DOI:10.1016/j.atherosclerosis.2024.118514]

22. Vafai S, Karsten V, Jensen C, Falzone R, Lister T, Stolz L, et al. Design of Heart-2: a phase 1b clinical trial of VERVE-102, an in vivo base editing medicine delivered by a GalNAc-LNP and targeting PCSK9 to durably lower LDL cholesterol. Circulation. 2024;150(Suppl_1):A4139206-A. https://www.ahajournals.org/doi/abs/10.1161/circ.150.suppl_1.4139206 DOI:10.1161/circ.150.suppl_1.4139206 [DOI:10.1161/circ.150.suppl_1.4139206]

23. Ding Q, Strong A, Patel KM, Ng S-L, Gosis BS, Regan SN, et al. Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. C Circ Res. 2014;115(5):488-92. https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.115.304351 [DOI:10.1161/CIRCRESAHA.115.304351] [PMID] []

24. Vogt A. Evinacumab in homozygous familial hypercholesterolemia caused by LDLRAP 1-first data of 2 unrelated cases. Atherosclerosis. 2024;395. https://www.atherosclerosis-journal.com/article/S0021-9150(24)00724-X/abstract DOI: 10.1016/j.atherosclerosis.2024.118157 [DOI:10.1016/j.atherosclerosis.2024.118157]

25. Lucero D, Dikilitas O, Mendelson MM, Aligabi Z, Islam P, Neufeld EB, et al. Transgelin: a new gene involved in LDL endocytosis identified by a genome-wide CRISPR-Cas9 screen. J J Lipid Res. 2022;63(1):100160. https://www.sciencedirect.com/science/article/pii/S0022227521001437 [DOI:10.1016/j.jlr.2021.100160] [PMID] []

26. Nedeljković E. The frequency of SLCO1B1 c. 388A> G and SLCO1B1 c. 521T> C polymorphisms in the Croatian population: University of Rijeka. Faculty of Biotechnology and Drug Development; 2024. https://repository.biotech.uniri.hr/islandora/object/biotechri:1075 https://urn.nsk.hr/urn:nbn:hr:193:605695

27. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681-90. https://jamanetwork.com/journals/jama/article-abstract/196305 https://pubmed.ncbi.nlm.nih.gov/12672737/ [DOI:10.1001/jama.289.13.1681] [PMID]

28. Abramson A, Frederiksen MR, Vegge A, Jensen B, Poulsen M, Mouridsen B, et al. Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors.Nat Biotechnol. 2022;40(1):103-9. https://www.nature.com/articles/s41587-021-01024-0 [DOI:10.1038/s41587-021-01024-0] [PMID] []

29. Nie T, Heo Y-A, Shirley M. Vutrisiran: a review in polyneuropathy of hereditary transthyretin-mediated amyloidosis. Drugs. 2023;83(15):1425-32. https://link.springer.com/article/10.1007/s40265-023-01943-z https://pubmed.ncbi.nlm.nih.gov/37728865/ [DOI:10.1007/s40265-023-01943-z] [PMID]