•  
  •  
 

ORCID ID

Loury Priskila: 0009-0007-3633-3543

Lenggana Relung Atmadi: 0009-0007-5926-0543

Arya Taksya Bagaskara: 0009-0008-0423-7423

Andreas Mercyan Anggitama: 0009-0005-0560-5732

Abstract

Background: Stroke is the second leading cause of mortality worldwide. In Yogyakarta, Indonesia, the incidence of stroke (14%) is higher than the national average. We therefore investigated the roles of LDLR rs688 (C/T) and PCSK9 rs562565 (A/G) polymorphisms in familial hypercholesterolemia as predictors of first-time ischemic stroke.

Methods: In this case-control study, 119 first-time ischemic stroke patients were divided into dyslipidemia (N = 71) and non-dyslipidemia groups (N = 48). The DNA of the nucleotide polymorphisms LDLR rs688 (C/T) and PCSK9 rs562556 (A/G) was extracted and analyzed using the PCR-RFLP method, and statistical analyses were performed to evaluate their predictive potential.

Results: The LDLR rs688 (C/T) CT genotype was the most common in both groups. The TT genotype appeared slightly more frequently in the dyslipidemia group, but no significant association was found with dyslipidemia (p = 0.460). While lipid levels had no significant relationship with LDLR rs688 (C/T), hemoglobin levels differed significantly across the genotypes (p = 0.002), which suggested the biological relevance of hemoglobin.

Conclusions: The LDLR rs688 (C/T) polymorphism was not significantly associated with dyslipidemia among the stroke patients. Nonetheless, genotype-related trends related to lipid and hemoglobin levels indicated potential mechanisms that warrant further investigation.

References

  1. Turana Y, Tengkawan J, Chia YC, Nathaniel M, Wang JG, Sukonthasarn A, et al. Hypertension and stroke in Asia: A comprehensive review from HOPE Asia. J Clin Hypertens. 2021;23:513–21.
  2. Tadi P, Lui F. Acute stroke. Treasure Island (FL): StatPearls Publishing; 2025.
  3. Donkor ES. Stroke in the 21st century: A snapshot of the burden, epidemiology, and quality of life. Stroke Res Treat. 2018;2018:3238165.
  4. Feigin VL, Vos T. Global burden of neurological disorders: From global burden of disease estimates to actions. Neuroepidemiology. 2019;52:1–2.
  5. Pu L, Wang L, Zhang R, Zhao T, Jiang Y, Han L. Projected global trends in ischemic stroke incidence, deaths and disability-adjusted life years from 2020 to 2030. Stroke. 2023;54:1330–9.
  6. Baba M, Maris M, Jianu D, Luca CT, Stoian D, Mozos I. The impact of the blood lipids levels on arterial stiffness. J Cardiovasc Dev Dis. 2023;10:127.
  7. Fekadu G, Chelkeba L, Kebede A. Risk factors, clinical presentations and predictors of stroke among adult patients admitted to stroke unit of Jimma University medical center, South West Ethiopia: Prospective observational study. BMC Neurol. 2019;19:187.
  8. Sabih QA, Young J, Takabe K. Management of male breast cancer: The journey so far and future directions. World J Oncol. 2021;12:206–13.
  9. Roy-O’Reilly M, McCullough LD. Age and sex are critical factors in ischemic stroke pathology. Endocrinology. 2018;159:3120–31.
  10. Yousufuddin M, Young N. Aging and ischemic stroke. Aging. 2019;11:2542–4.
  11. Jacob MA, Ekker MS, Allach Y, Cai M, Aarnio K, Arauz A, et al. Global differences in risk factors, etiology, and outcome of ischemic stroke in young adults-A worldwide meta-analysis: The GOAL Initiative. Neurology. 2022;98:e573–88.
  12. Khadka T, Giri GK, Sherpa P, Ghimire U, Parajuli S, Pudasaini A, et al. Dyslipidemia among patients with ischemic stroke admitted to the department of medicine of a tertiary care centre. JNMA J Nepal Med Assoc. 2023;61:718–22.
  13. Kloska A, Malinowska M, Gabig-Cimińska M, Jakóbkiewicz-Banecka J. Lipids and Lipid mediators associated with the risk and pathology of ischemic stroke. Int J Mol Sci. 2020;21:3618.
  14. Feingold KR. Introduction to lipids and lipoproteins. In: Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2024.
  15. Pirahanchi Y, Sinawe H, Dimri M. Biochemistry, LDL cholesterol. Treasure Island (FL): StatPearls Publishing; 2025.
  16. Yang H-x, Zhang M, Long S-y, Tuo Q-h, Tian Y, Chen J-x, et al. Cholesterol in LDL receptor recycling and degradation. Clinica Chimica Acta. 2020;500:81–6.
  17. Hasheminasabgorji E, Jha JC. Dyslipidemia, diabetes and atherosclerosis: Role of inflammation and ros-redox-sensitive factors. Biomedicines. 2021;9:1602.
  18. Dai Z, Wang Y, Li P, Zhang H, Gou X. The association between polymorphism of LDL-R gene and ischemic stroke risk in Chinese population: A meta-analysis. Heliyon. 2024;10:e26314.
  19. Ferreira JP, Xhaard C, Lamiral Z, Borges‐Canha M, Neves JS, Dandine‐Roulland C, et al. PCSK9 Protein and rs562556 Polymorphism Are associated with arterial plaques in healthy middle‐aged population: The STANISLAS Cohort. J Am Heart Assoc. 2020;9:e014758.
  20. Hashim HO, Al-Shuhaib MB. Exploring the potential and limitations of PCR-RFLP and PCR-SSCP for SNP detection: A review. J Apple Biotechnol Rep. 2019;6:137–44.
  21. Muneeswaran K, De Silva VA, Branavan U, Dayabandara M, Hanwella R, Chandrasekharan NV. PCR-based SNP genotyping: A comprehensive comparison of methods for affordable and accurate detection of class IV mutations. Analytica Chimica Acta. 2025;1354:343994.
  22. Kim Y, Choi SJ, Choi C. An efficient PCR-RFLP Method for the rapid identification of Korean Pyropia species. Molecules. 2017;22:2182.
  23. Buraczynska M, Jacob J, Gwiazda-Tyndel K, Ksiazek A. LDLR gene polymorphism (rs688) affects susceptibility to cardiovascular disease in end-stage kidney disease patients. BMC Nephrol. 2021;22:316.
  24. Devi K, Bhargave A, Ahmad I, Yadav A, Gupta R. Association study of PCSK9 SNPs (rs505151 & rs562556) and their haplotypes with CVDs in Indian population. Ann Hum Biol. 2023;50:56–62.
  25. Eren K, Taktakoğlu N, Pirim I. DNA sequencing methods: From past to present. Eurasian J Med. 2022;54:47–56.
  26. Desai A, Oh D, Rao EM, Sahoo S, Mahajan UV, Labak CM, et al. Impact of anemia on acute ischemic stroke outcomes: A systematic review of the literature. Thanachartwet V, editor. PLoS One. 2023;18:e0280025.
  27. Al-Harbi N, Alrasheedi MS, Alshammari ST. Hemoglobin level is associated with severe stroke among stroke patients in Saudi Arabia. Int J Health Sci. 2020;14:18–22.
  28. Barlas RS, Honney K, Loke YK, McCall SJ, Bettencourt‐Silva JH, Clark AB, et al. Impact of hemoglobin levels and anemia on mortality in acute stroke: Analysis of UK Regional registry data, systematic review, and meta‐analysis. J Am Heart Assoc. 2016;5:e003019.
  29. Kellert L, Martin E, Sykora M, Bauer H, Gussmann P, Diedler J, et al. Cerebral oxygen transport failure?: Decreasing hemoglobin and hematocrit levels after ischemic stroke predict poor outcome and mortality: STroke: RelevAnt Impact of hemoGlobin, Hematocrit and Transfusion (STRAIGHT)—an Observational Study. Stroke. 2011;42:2832–7.
  30. Zhang R, Xu Q, Wang A, Jiang Y, Meng X, Zhou M, et al. Hemoglobin concentration and clinical outcomes after acute ischemic stroke or transient ischemic attack. J Am Heart Assoc. 2021;10:e022547.
  31. Tanne D, Molshatzki N, Merzeliak O, Tsabari R, Toashi M, Schwammenthal Y. Anemia status, hemoglobin concentration and outcome after acute stroke: A cohort study. BMC Neurol. 2010;10:22.
  32. Abuhulayqah S, Aldulijan FA, Turkistani AN, Almulhim AF, Almulhim CF, Bashir S, et al. Impact of hemoglobin levels on acute ischemic stroke severity. Front Neurol. 2025;16:1534746.
  33. Andone S, Farczádi L, Imre S, Bălașa R. Fatty acids and lipid paradox-neuroprotective biomarkers in ischemic stroke. Int J Mol Sci. 2022;23:10810.

Creative Commons License

Creative Commons Attribution-Share Alike 4.0 International License
This work is licensed under a Creative Commons Attribution-Share Alike 4.0 International License.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.