Genetic Polymorphism of ITGA2 C807T Collagen Receptor Encoding Gene of Aspirin Therapy among Javanese-Indonesian Healthy Respondents

Authors

  • Vitarani Dwi Ananda Ningrum Department of Pharmacy, Laboratory of Pharmaceutical Research, Universitas Islam Indonesia, Yogyakarta, Indonesia https://orcid.org/0000-0003-0423-5555
  • Rochmy Istikharah Department of Pharmacy, Laboratory of Biochemistry, Universitas Islam Indonesia, Yogyakarta, Indonesia
  • Ahmad H. Sadewa Department of Biochemistry, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7430

Keywords:

Aspirin, Integrin Alpha-2, C807T polymorphism, Javanese-Indonesian

Abstract

BACKGROUND: Aspirin is an antiplatelet drug commonly administered as primary and secondary prophylaxis to prevent thromboembolic events. However, there has been a common incidence of aspirin resistance that leads to a recurrent cerebrovascular disease. One of the causes of such event is the genetic polymorphisms of the integrin alpha-2 (ITGA2) gene that encodes the glycoprotein Ia (GPIa) receptor in the pharmacodynamics of aspirin.

AIM: This study analyzed the genetic polymorphism of ITGA2 as the GPIa collagen receptor encoding gene of aspirin therapy among healthy Javanese, the largest ethnic group in Indonesia.

METHODS: This cross-sectional study involved 100 respondents who met the inclusion criteria with their blood sample taken for DNA isolation. Identification of genetic polymorphism in the target SNPs was done using the PCR-RFLP method with 5’-CCTTAAAGCTACCGGCCCATGT-3’ forward primer and 5’-TTGGCCTATTAGCACCAAAACTTACC-3’ reverse primer as well as Hpy188Irestriction enzyme to fragment the target at position 244 in the C base.

RESULTS: This study found that the dominant genotype and allele were CT (51%) and C (66.5%), respectively.

CONCLUSION: The allele frequency of ITGA2 gene in this study was similar to that of the populations in other Asian countries. Further research regarding the effects of ITGA2 C807T polymorphism on the pharmacodynamics of aspirin as an antiplatelet is recommended to minimize atherothrombotic events and examine its interactions as a biomarker of the risk and prognosis of some cancer types.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Goodman T, Ferro A, Sharma P. Pharmacogenetics of aspirin resistance: A comprehensive systematic review. Br J Clin Pharmacol 2008;66(2):222-32. https://doi.org/10.1111/j.1365-2125.2008.03183.x PMid:18429969 DOI: https://doi.org/10.1111/j.1365-2125.2008.03183.x

Ittaman SV, VanWormer JJ, Rezkalla SH. The role of aspirin in the prevention of cardiovascular disease. Clin Med Res. 2014;12(3-4):147-54. https://doi.org/10.3121/cmr.2013.1197 PMid:24573704 DOI: https://doi.org/10.3121/cmr.2013.1197

Grinstein J, Cannon CP. Aspirin resistance: Current status and role of tailored therapy. Clin Cardiol. 2012;35(11):673-80. https://doi.org/10.1002/clc.22031 PMid:22740110 DOI: https://doi.org/10.1002/clc.22031

FitzGerald R, Pirmohamed M. Aspirin resistance: Effect of clinical, biochemical and genetic factors. Pharmacol Ther. 2011;130(2):213-25. https://doi.org/10.1016/j.pharmthera.2011.01.011 PMid:21295071 DOI: https://doi.org/10.1016/j.pharmthera.2011.01.011

Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin “resistance” and risk of cardiovascular morbidity: Systematic review and meta-analysis. BMJ. 2008;336(7637):195-8. https://doi.org/10.1136/bmj.39430.529549.BE PMid:18202034 DOI: https://doi.org/10.1136/bmj.39430.529549.BE

Floyd CN, Ferro A. Mechanisms of aspirin resistance. Pharmacol Ther. 2014;141(1):69-78. https://doi.org/10.1016/j.pharmthera.2013.08.005 PMid:23993980 DOI: https://doi.org/10.1016/j.pharmthera.2013.08.005

Wang H, Sun X, Dong W, Cai X, Zhou Y, Zhang Y, et al. Association of GPIa and COX-2 gene polymorphism with aspirin resistance. J Clin Lab Anal. 2018;32(4):e22331. https://doi.org/10.1002/jcla.22331 PMid:28948649 DOI: https://doi.org/10.1002/jcla.22331

Weng Z, Li X, Li Y, Lin J, Peng F, Niu W. The association of four common polymorphisms from four candidate genes (COX- 1, COX-2, ITGA2B, ITGA2) with aspirin insensitivity: A meta-analysis. PLoS One. 2013;8:e78093. PMid:24244288 DOI: https://doi.org/10.1371/journal.pone.0078093

Wu G, Xi Y, Yao L, Su L, Yan Y, Li M, et al. Genetic polymorphism of ITGA2 C807T can increase the risk of ischemic stroke. Int J Neurosci 2014;124(11):841-51. https://doi.org/10.3109/00207454.2013.879718 PMid:24397542 DOI: https://doi.org/10.3109/00207454.2013.879718

Lu JX, Lu ZQ, Zhang S, Zhi J, Chen ZP, Wang WX. Polymorphism in integrin ITGA2 is associated with ischemic stroke and altered serum cholesterol in Chinese individuals. Balkan Med J. 2014;31(1):55-9. https://doi.org/10.5152/balkanmedj.2013.7993 PMid:25207168 DOI: https://doi.org/10.5152/balkanmedj.2013.7993

Liu H, Wang Y, Zheng J, Li G, Chen T, Lei J, et al. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα _VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis. Int J Stroke. 2017;12:46-70. https://doi.org/10.1177/1747493016672085 PMid:28004990 DOI: https://doi.org/10.1177/1747493016672085

Holsinger KE. Hardy-Weinberg Law. Encyclopedia of Genetics. Amsterdam, Netherlands: Elsevier; 2001. p. 912-4. https://doi.org/10.1006/rwgn.2001.0585 DOI: https://doi.org/10.1006/rwgn.2001.0585

Rogers AJ, Weiss ST. Epidemiologic and population genetic studies. In: Clinical and Translational Science. Amsterdam, Netherlands: Elsevier; 2017. p. 313-26. https://doi.org/10.1016/B978-0-12-802101-9.00017-X DOI: https://doi.org/10.1016/B978-0-12-802101-9.00017-X

Faraday N, Goldschmidt-Clermont PJ, Bray PF. Gender differences in platelet GPIIb-IIIa activation. Thromb Haemost. 1997;77(4):748-54. PMid:9134654 DOI: https://doi.org/10.1055/s-0038-1656045

Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: A sex-specific meta-analysis of randomized controlled trials. JAMA. 2006;295(3):306-13. https://doi.org/10.1001/jama.295.3.306 PMid:16418466 DOI: https://doi.org/10.1001/jama.295.3.306

Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293-304. https://doi.org/10.1056/NEJMoa050613 PMid:15753114 DOI: https://doi.org/10.1056/NEJMoa050613

Franconi F, Campesi I. Pharmacogenomics, pharmacokinetics and pharmacodynamics: Interaction with biological differences between men and women. Br J Pharmacol. 2014;171(3):580-94. https://doi.org/10.1111/bph.12362 PMid:23981051 DOI: https://doi.org/10.1111/bph.12362

Kvasnicka T, Bobcikova P, Malikova I, Hajkova J, Zima T, Ulrych J, et al. The frequencies of ten platelet polymorphisms associated with atherosclerotic cardiovascular disease in patients with venous thromboembolism: A population-based case-control study. Hereditary Genet. 2015;4:153. https://doi.org/10.4172/2161-1041.1000153 DOI: https://doi.org/10.4172/2161-1041.1000153

Zhang JH, Wang J, Tang XF, Yao Y, Zhang Y, Ma YL, et al. Effect of platelet receptor gene polymorphisms on outcomes in ST-elevation myocardial infarction patients after percutaneous coronary intervention. Platelets. 2016;27(1):75-9. https://doi.org/10.3109/09537104.2015.1034096 PMid:25901734 DOI: https://doi.org/10.3109/09537104.2015.1034096

Al-Azzam SI, Alzoubi KH, Khabour OF, Tawalbeh D, Al-Azzeh O. The contribution of platelet glycoproteins (GPIa C807T and GPIba C-5T) and cyclooxygenase 2 (COX-2G-765C) polymorphisms to platelet response in patients treated with aspirin. Gene. 2013;526(2):118-21. https://doi.org/10.1016/j.gene.2013.04.083 PMid:23688555 DOI: https://doi.org/10.1016/j.gene.2013.04.083

Liakhotska A. Genetic features of resistance to antithrombocytic drugs in patients with ischemic heart disease after conducted percutaneous coronary intervention. EUREKA. 2017;6:35-41. https://doi.org/10.21303/2504-5679.2017.00490 DOI: https://doi.org/10.21303/2504-5679.2017.00490

Cole VJ, Staton JM, Eikelboom JW, Hankey GJ, Yi Q, Shen Y, et al. Collagen platelet receptor polymorphisms integrin α2β1 C807T and GPVI Q317L and risk of ischemic stroke. J Thromb Haemostasis. 2003;1(5):963-70. https://doi.org/10.1046/j.1538-7836.2003.00179.x PMid:12871362 DOI: https://doi.org/10.1046/j.1538-7836.2003.00179.x

Rath D, Schaeffeler E, Winter S, Levertov S, Müller K, Droppa M, et al. GPla polymorphisms are associated with outcomes in patients at high cardiovascular risk. Front Cardiovasc Med. 2017;4:52. https://doi.org/10.3389/fcvm.2017.00052 PMid:28871283 DOI: https://doi.org/10.3389/fcvm.2017.00052

Martínez C, Antón AI, Corral J, Quiroga T, Panes O, Lozano ML, et al. Genotype-phenotype relationship for six common polymorphisms in genes affecting platelet function from 286 healthy subjects and 160 patients with mucocutaneous bleeding of unknown cause. Br J Haematol. 2009;146(1):95-103. https://doi.org/10.1111/j.1365-2141.2009.07713.x PMid:19388931 DOI: https://doi.org/10.1111/j.1365-2141.2009.07713.x

Verschuren JJW, Boden H, Wessels JA, van der Hoeven BL, Trompet S, Heijmans BT, et al. Value of platelet pharmacogenetics in common clinical practice of patients with ST-segment elevation myocardial infarction. Int J Cardiol. 2013;167(6):2882- 8. https://doi.org/10.1016/j.ijcard.2012.07.020 PMid:22940005 DOI: https://doi.org/10.1016/j.ijcard.2012.07.020

Liu H, Xu Z, Gu H, Li W, Chen W, Sun C, et al. Common variant in glycoprotein ia increases long‐term adverse events risk after coronary artery bypass graft surgery. J Am Heart Assoc. 2016;5(12):e004496. https://doi.org/10.1161/JAHA.116.004496 PMid:27881421 DOI: https://doi.org/10.1161/JAHA.116.004496

Sionova M, Blasko P, Jirous S, Vindis D, Rokyta R, Motovska Z. Association of polymorphisms of platelet receptors GPIa (807C>T), GPVI (13254T>C), and P2Y12 (34C>T and H1/ H2 haplotype) with increased risk of periprocedural bleeding in patients undergoing coronary angiography/percutaneous coronary intervention. Postepy Kardiol Interwencyjnej. 2017;13(3):202-9. https://doi.org/10.5114/aic.2017.70187 PMid:29056992 DOI: https://doi.org/10.5114/aic.2017.70187

Mukarram O, Akhtar N, Junaid A, Mohyuddin A. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease. Pak J Pharm Sci. 2016;29(4):1177-82. PMid:27393450

Fujiwara T, Ikeda M, Esumi K, Fujita TD, Kono M, Tokushige H, et al. Exploratory aspirin resistance trial in healthy Japanese volunteers (J-ART) using platelet aggregation as a measure of thrombogenicity. Pharmacogenomics J. 2007;7(6):395-403. https://doi.org/10.1038/sj.tpj.6500435 PMid:17245331 DOI: https://doi.org/10.1038/sj.tpj.6500435

Chen J, Liu NN, Li JQ, Yang L, Zeng Y, Zhao XM, et al. Association between ITGA2 C807T polymorphism and gastric cancer risk. World J Gastroenterol. 2011;17(23):2860-6. https://doi.org/10.3748/wjg.v17.i23.2860 PMid:21734795

Ballesteros F, Tassies D, Reverter JC, Alobid I, Bernal-Sprekelsen M. Idiopathic sudden sensorineural hearing loss: Classic Cardiovascular and new genetic risk factors. Audiol Neurootol. 2012;17(6):400-8. https://doi.org/10.1159/000341989 PMid:22948415 DOI: https://doi.org/10.1159/000341989

Filippova OA, Vakhlova IV, Tsaur GA, Kuznetsov NN, Abolina TB. The role of thrombophilia genes in the clinical implementation of arterial and venous thrombosis in newborns. BIO Web Conf. 2020;22:02021. https://doi.org/10.1051/bioconf/20202202021 DOI: https://doi.org/10.1051/bioconf/20202202021

Golovchenko OV, Abramova MY, Altukhova OB, Verzilina IN, Rudyh NA, Kulikovsky VF. The role of polymorphism of hereditarythrombophilia candidate genes in the development of arterial hypertension in women with preeclampsia. Syst Rev Pharm. 2020;11(6):11-5.

Gerger A, Hofmann G, Langsenlehner U, Renner W, Weitzer W, Wehrschütz M, et al. Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk. Int J Colorectal Dis. 2009;24(2):159-63. https://doi.org/10.1007/s00384-008-0587-9 PMid:18836731 DOI: https://doi.org/10.1007/s00384-008-0587-9

Ban EZ, Lye MS, Chong PP, Yap YY, Lim SY, Rahman HA. Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients. PLoS One. 2018;13(6):e0198332. https://doi.org/10.1371/journal.pone.0198332 DOI: https://doi.org/10.1371/journal.pone.0198332

Simou M, Kouskouni E, Vitoratos N, Economou E, Creatsas G. Polymorphisms of platelet glycoprotein receptors and cell adhesion molecules in fetuses with fetal growth restriction and their mothers as detected with pyrosequencing. In Vivo. 2017;31(2):243-9. https://doi.org/10.21873/invivo.11052 PMid:28358707 DOI: https://doi.org/10.21873/invivo.11052

Tsantes AE, Nikolopoulos GK, Bagos PG, Vaiopoulos G, Travlou A. Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: A meta-analysis. Int J Cardiol. 2007;118(2):189-96. https://doi.org/10.1016/j.ijcard.2006.06.047 PMid:17023078 DOI: https://doi.org/10.1016/j.ijcard.2006.06.047

Madamanchi A, Santoro SA, Zutter MM. α2β1 integrin. Adv Exp Med Biol. 2014;819:41-60. https://doi.org/10.1007/978-94-017-9153-3_3 PMid:25023166 DOI: https://doi.org/10.1007/978-94-017-9153-3_3

Adorno-Cruz V, Liu H. Regulation and functions of integrin α2 in cell adhesion and disease. Genes Dis. 2018;6(1):16-24. https://doi.org/10.1016/j.gendis.2018.12.003 PMid:30906828 DOI: https://doi.org/10.1016/j.gendis.2018.12.003

Downloads

Published

2021-11-25

How to Cite

1.
Ningrum VDA, Istikharah R, Sadewa AH. Genetic Polymorphism of ITGA2 C807T Collagen Receptor Encoding Gene of Aspirin Therapy among Javanese-Indonesian Healthy Respondents. Open Access Maced J Med Sci [Internet]. 2021 Nov. 25 [cited 2024 Mar. 28];9(A):1067-73. Available from: https://oamjms.eu/index.php/mjms/article/view/7430