Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals

Öz

Background: Recent studies have reported contrasting results regarding the association of polymorphisms in two integrin genes, ITGA2 and ITGB3, with ischemic stroke. Aims: The present study aimed to investigate the correlation between the ITGA2 C807T and ITGB3 T176C polymorphic loci with ischemic stroke, as well as plasma lipid and lipoprotein levels. Study Design: Case control study. Methods: Human venous blood samples were collected from patients admitted for ischemic stroke (n=350, ‘patients') and healthy individuals (n=300, ‘controls'). Blood was genotyped at these loci by polymerase chain reaction-restriction fragment length polymorphism. Plasma lipid and lipoprotein levels were measured by routine enzymatic, masking, and turbidimetry methods. Results: As expected, total cholesterol, triglycerides, and low-density lipoprotein were all significantly higher in patients than in controls (p<0.05). Genotype and allele frequencies of ITGA2 C807T were significantly different between patients and controls (p<0.05), but no difference was detected in genotype or allele frequencies for ITGA3 T176C. For ITGA-2, the T allele conferred a 1.226 times higher relative risk of ischemic stroke than the C allele (odds ratio=1.226, 95% confidence interval=1.053–1.428). Similarly, total cholesterol was higher in T allele carriers than in non-carriers (p<0.05). Conclusion: ITGA2 C807T polymorphism is associated with ischemic stroke, with the T allele acting as a susceptibility allele that appears to confer increased cholesterol levels.

Anahtar Kelimeler

• Gene polymorphism, Integrin α2, Integrin β3, ischemic stroke, plasma lipid

Polymorphism in Integrin ITGA2 is Associated with Ischemic Stroke and Altered Serum Cholesterol in Chinese Individuals

Öz

Kaynakça

1. Meschia JF, Worrall BB, Rich SS. Genetic susceptibility to ischemic stroke. Nat Rev Neurol 2011;7:369-78. [CrossRef]
2. Huo Y, Ley K. Adhesion molecules and atherogenesis. Acta Physiol Scand 2001;173:35-43. [CrossRef]
3. Elkind MS. Inflammation, atherosclerosis, and stroke. Neurologist 2006;12:140-8. [CrossRef]
4. Rivera J, Lozano ML, Navarro-Nş-ez L, Vicente V. Platelet receptors and signaling in the dynamics of thrombus formation. Haematologica 2009;94:700-11. [CrossRef]
5. Nikolopoulos GK, Tsantes AE, Bagos PG, Travlou A, Vaiopoulos G. In- tegrin, alpha 2 gene C807T polymorphism and risk of ischemic stroke:a meta-analysis. Thromb Res 2007;119:501-10. [CrossRef]
6. Wei YS, Lan Y, Liu YG, Meng LQ, Xu QQ, Xie HY. Association of the integrin gene polymorphisms with ischemic stroke and plasma lipid levels. Zhonghua Yi Xue Yi Chuang Xue Za Zhi 2009;26:211-5.
7. Reiner AP, Kumar PN, Schwartz SM, Longstreth WT Jr, Pearce RM, Rosendaal FR, et al. Genetic variants of platelet glycoprotein receptors and risk of stroke in young women. Stroke 2000;31:1628-33. [CrossRef]
8. Maakaroun A, Regina S, Delahousse B, Saudeau D, Gruel Y. Ischemic strokes and homozygosity for the alpha2 807T allele of the platelet collagen receptor in young monozygotic twins. Blood Coagul Fibrinolysis 2003;14:83-5. [CrossRef]

9. Matarin M, Brown WM, Hardy JA, Rich SS, Singleton AB, Brown RD Jr, et al. Association of integrin alpha gene variants with ischemic stroke. J Cereb Blood Flow Metab 2008;28:81-9. [CrossRef]
10. Xavier UR, Joaquín SL. Stoke, diagnosis and therapeutic management of cerebrovascular disease. Rev Esp Cardiol 2007;60:753-69.
11. Orii KE, Aoyama T, Wakui K, Fukushima Y, Miyajima H, Yamaguchi S, et al. Genomic and Mutational Analysis of the Mitochondrial Trifunctional Protein β-Subunit (HADHB) Gene in Patients with Trifunctional Protein Deficiency. Hum Mol Genet 1997;6:1215-24. [CrossRef]
12. Hellewell PG. Adhesion molecule strategies. Pulm Pharmacol Ther 1999;12:137-41. [CrossRef]
13. Jacquelin B, Rozenshteyn D, Kanaji S, Koziol JA, Nurden AT, Kunicki TJ. Characterization of Inherited Differences in Transcription of the Human In- tegrin alpha 2 Gene. J Biol Chem 2001;276:23518-24. [CrossRef]
14. Vijayan KV, Liu Y, Dong JF, Bray PF. Enhanced activation of mitogen-ac- tivated protein kinase and myosin light chain kinase by the Pro33 polymor- phism of integrin beta 3. J Biol Chem 2003;278:3860-7. [CrossRef]
15. Payne KE, Bray PF, Grant PJ, Carter AM. Beta3 integrin haplotype influences gene regulation and plasma von Willebrand factor activity. Atherosclerosis 2008;198:280-6. [CrossRef]
16. Manginas A, Tsiavou A, Chaidaroglou A, Giamouzis G, Degiannis D, Pan- agiotakos D, et al. Inflammatory cytokine gene variants in coronary artery disease patients in Greece. Coron Artery Dis 2008;19:575-82. [CrossRef]
17. Giusti B, Gori AM, Marcucci R, Sestini I, Saracini C, Paniccia R, et al. Role of glycoprotein Ia gene polymorphisms in determining plate- let function in myocardial infarction patients undergoing percutaneous coronary intervention on dual antiplatelet treatment. Atherosclerosis 2008;196:341-8. [CrossRef]