Serebrovasküler hastalıklar ile insan lökosit antijen alt grupları arasındaki ilişki

Yıl 2023, Cilt: 16 Sayı: 2, 318 - 324, 05.04.2023

Ufuk Çınkır Eylem Teke Ergun Mete

https://doi.org/10.31362/patd.1263788

Öz

Amaç: İskemik inme, büyük arter aterosklerozu, küçük damar tıkanıklığı (laküner enfarktlar), diğer tanımlanmış
nedenlere bağlı iskemik inme ve kriptojenik olarak sınıflandırılır. İnsan lökosit antijeni (HLA) kompleksi insanlarda
bağışıklık sistemini düzenleyen hücre yüzeyi proteinlerini kodlamaktan sorumlu, altıncı kromozom üzerinde yer
alan bir grup gendir. Bu araştırmada, HLA'nın iskemik inme patofizyolojisindeki özellikle laküner alt gruptaki
rollerinin araştırılması ve olası mekanizmaların aydınlatması amaçlanmıştır.
Gereç ve yöntem: Bu çalışma iskemik inmeli 49 hasta ve 50 sağlıklı katılımcıdan oluşmaktadır. HLA-A, HLA-B,
HLA-C, HLA-DQB ve HLA-DRB alt grup genomları değerlendirilmiştir.
Bulgular: Kontrol ve hasta gruplarında HLA-A, HLA-B, HLA-C, HLA-DQB ve HLA-DRB alt gruplarının varlığı
arasında istatistiksel olarak anlamlı fark bulunmuştur. HLA-A*02, HLA-A*30, HLA-B*08, HLA-B*15 ve HLADQB*
06 genomları hasta grubunda daha fazla bulunmuştur ve istatistiksel olarak anlamlı fark vardır (p≤0.05).
Bununla birlikte HLA-DQB*03 ve HLA-DRB*11 genomları kontrol grubunda daha fazla bulunmuştur (p≤0.05).
Sonuç: Bu araştırma, küçük damar hastalığında (KDH) HLA alellerini incelemede öncüdür. HLA-A*01,
HLA-A*30, HLA-B*08, HLA-B*15, HLA-DQB*06, HLA-DQB*03, HLA-DRB*11, inme hastalarının HLA alelleri
ile ilişkilidir. Küçük damar tıkanıklığı HLA genomlarının, KDH hastaları ve kontrol grupları arasında, gelecekteki
tedaviler için umut vaat edebilecek, ayırt edici bir faktör olarak hareket edip edemeyeceğine dair nesnel kanıtlar
sağlamaya çalıştık.

Anahtar Kelimeler

Strok, major doku uygunluk kompleksi, genom, küçük damar hastalığı, iskemi

Destekleyen Kurum

PAMUKKALE ÜNİVERSİTESİ BİLİMSEL ARAŞTIRMALAR PROJESİ FONU

Proje Numarası

2018TIPF043

Relationship between cerebrovascular diseases and human leukocyte antigen subgroups

Öz

Abstract
Purpose: Ischemic stroke is classified as large artery atherosclerosis, small vessel occlusion (lacunar infarcts),
ischemic stroke due to other identified causes, and cryptogenic. The human leukocyte antigen (HLA) complex
is a group of genes on chromosome six in humans responsible for encoding cell-surface proteins that regulate
the immune system. In this study, HLA’s roles in the pathophysiology of ischemic stroke, especially the lacunar
subgroup, are investigated, and their potential mechanisms are presented.
Materials and methods: This study consisted of 49 patients with ischemic stroke and 50 healthy participants.
HLA-A, HLA-B, HLA-C, HLA-DQB, and HLA-DRB subgroup genomes were assessed.
Results: A statistically significant difference in the presence of HLA-A, HLA-B, HLA-C, HLA-DQB, and HLADRB
subgroups was found between the control and patient groups. The presence of HLA-A*02, HLA-A*30,
HLA-B*08, HLA-B*15, and HLA-DQB*06 genomes was higher in the patient group than in the control group
(p≤0.05). Nevertheless, HLA-DQB*03 and HLA-DRB*11 genomes were found more in the control group than
the patient group (p≤0.05)
Conclusion: The results of this study pioneered in scrutinizing HLA alleles in small vascular disease (SVD).
HLA-A*01, HLA-A*30, HLA-B*08, HLA-B*15, HLA-DQB*06, HLA-DQB*03 and HLA-DRB*11 are associated with
HLA alleles of stroke patients with small vessel occlusion. We attempted to provide objective evidence for
whether HLA genomes could act as a discriminative factor between SVD patients and control groups, which
might hold considerable promise for future therapies.

Anahtar Kelimeler

Stroke, major histocompatibility complex, genome, small vessel disease, ischemia

Proje Numarası

2018TIPF043

Kaynakça

• 1. Adams Jr HP, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke. definitions for use in a multicenter clinical trial. toast. trial of org 10172 in acute stroke treatment. Stroke 1993;24:35-41. https://doi.org/10.1161/01.str.24.1.35
• 2. Ozdemir G, Ozkan S, Uzuner N, Ozdemir O, Gucuyener D. Major risk factors for cerebrovascular diseases in Turkey: Turkish multicenter stroke study. Turkish Journal of Cerebrovascular Diseases 2000;6:31-35.
• 3. Thurman RJ, Jauch EC. Acute ischemic stroke: emergent evaluation and management. Emerg Med Clin North Am 2002;20:609-630. https://doi.org/10.1016/s0733-8627(02)00014-7
• 4. Griffiths D, Sturm J. Epidemiology and aetiology of young stroke. Stroke Res Treat 2011; 2011: 209370. https://doi.org/10.4061/2011/209370
• 5. Barnet H, Mohr J, Stein B, Yatsu FM. Stroke: Pathophysiology, diagnosis and management. 4th ed. New York: Churchill Livingstone, 1987;286.
• 6. Bonita R. Epidemiology of stroke. Lancet 1992;339:342-344. https://doi.org/10.1016/0140-6736(92)91658-u
• 7. Sudlow CLM, Warlow CP. Comparing stroke incidence worldwide: what makes studies comparable? Stroke 1996;27:550-558. https://doi.org/10.1161/01.STR.27.3.550
• 8. Wolf PA, Belanger AJ, D’Agostino RB. Management of risk factors. Neurologic Clinics 1992;10:177-191. https://doi.org/10.1016/S0733-8619(18)30240-8
• 9. Kumral E, Ozkaya B, Sagduyu A, Sirin H, Vardarli E, Pehlivan M. The Aegean stroke registry: a hospital-based study in the Aegean region, Izmir, Turkey, analysis of 2.000 stroke patients. Cerebrovasc Dis 1998;8:278-88. https://doi.org/10.1159/000015866
• 10. Kabakcı G, Abacı A, Ertas FS, Ozerkan F, Erol C, Oto A. The risk for stroke and differences among geographical regions regarding this risk in hypertensive patients in Turkey: a hospital-based, cross-sectional, epidemiological questionnaire (THINK) study). Turkish Society of Cardiology Archives 2006;34:395-405.
• 11. Ringleb PA, Bousser MG, Ford G, et al. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovascular Diseases 2008;25:457-507. https://doi.org/10.1159/000131083
• 12. Hankey GJ. Potential new risk factors for ischemic stroke: what is their potential? Stroke 2006;37:2181-2188. https://doi.org/10.1161/01.STR.0000229883.72010.e4
• 13. Laskowitz DT, Kasner SE, Saver J, Remmel KS, Jauch EC, Group BS. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the biomarker rapid assessment in ischemic injury (BRAIN) study. Stroke 2009;40:77-85. https://doi.org/10.1161/STROKEAHA.108.516377
• 14. Shiina T, Hosomichi K, Inoko H, Kulski JK. The HLA genomic loci map: expression, interaction, diversity, and disease. J Hum Genet 2009;54:15-39. https://doi.org/10.1038/jhg.2008.5
• 15. Purcell SM, Wray NR, Stone JL, et al. Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 2009;10:8192. https://doi.org/10.1038/nature08185
• 16. Song S, Miranda CJ, Braun L, et al. Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis (ALS). Nat Med 2016;22:397-403. https://doi.org/10.1038/nm.4052
• 17. Shatz CJ. MHC class I: an unexpected role in neuronal plasticity. Neuron 2009;64:40-45. https://doi.org/10.1016/j.neuron.2009.09.044
• 18. Hamza TH, Zabetian CP, Tenesa A, et al. Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson’s disease. Nat Genet 2010;42:781-785. https://doi.org/10.1038/ng.642
• 19. Hill Burns EM, Factor SA, Zabetian CP, Thomson G, Payami H. Evidence for more than one Parkinson’s disease-associated variant within the HLA region. PLoS One 2011;6:e27109. https://doi.org/10.1371/journal.pone.0027109
• 20. Lewandowski C, Barsan W. Treatment of acute ischemic stroke. Ann Emerg Med 2001;37:202-216. https://doi.org/10.1067/mem.2001.111573
• 21. Pirim I, Atasoy M, Ikbal M, Erdem T, Aliagaoglu C. HLA class I and class II genotyping in patients with Behcet’s disease: a regional study of the eastern part of Turkey. Tissue Antigens 2004;64:293-297. https://doi.org/10.1111/j.1399-0039.2004.00280.x
• 22. Kang EH, Kim JY, Takeuchi F, et al. Associations between the HLA-A polymorphism and the clinical manifestations of Behcet’s disease. Arthritis Res Ther 2011;13:49. https://doi.org/10.1186/ar3292
• 23. Kraemer M, Horn PA, Roder C, et al. Analysis of human leucocyte antigen genes in caucasian patients with idiopathic moyamoya angiopathy. Acta Neurochir (Wien) 2012;154:445-454. https://doi.org/10.1007/s00701-011-1261-5
• 24. Sayad A, Akbari MT, Inoko H, et al. Association between human leucocyte antigen alleles and risk of stroke in Iranian population. Int J Immunogenet 2019;46:179-191. https://doi.org/10.1111/iji.12421
• 25. Chen W, Feng H, Xu M, et al. Correlation study between ischemic stroke and polymorphism of human leucocyte antigen gene. Zhonghua Yi Xue Za Zhi 2014;94:499-502.