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Down Sendromlu Hastalarda Kalıtsal Protrombotik Risk Faktörlerinin Sıklığı

Year 2021, Volume: 13 Issue: 1, 89 - 93, 11.03.2021

İbrahim Halil Damar Recep Eröz Önder Kiliçaslan

https://doi.org/10.18521/ktd.823900
Cited By: 2

Abstract

Amaç: Down Sendromu (DS), kromozom 21 trizomisi olarak tanımlanır ve kardiyovasküler sistem hastalıkları ile ilişkilidir. Biz DS'li hastalarda kalıtsal trombofili genlerini (MTHFR A1298C, MTHFR C677T, Factor II G20210A, Factor V Leiden G1691A, Factor V Cambridge G1091C, Factor XIII, APOB, ITGB3, FVHR2, FGB, PAI-1 ve ACE) incelemeyi amaçladık.

Yöntem: Çalışmaya toplam 53 DS'lu hasta (32 erkek ve 21 kadın) dahil edildi. Olguların demografik, laboratuvar ve klinik özellikleri kaydedildi. 12 derivasyonlu Elektrokardiyogram (EKG), transtorasik ekokardiyografi ve kalıtsal trombofili genleri değerlendirildi.

Bulgular: Hastaların klinik ve gelişimsel kusur bulguları yüksekti. Hastaların % 39,6'sı hem heterozigot MTHFR C677T hem de heterozigot MTHFR A1298C taşıyıcısı, hastaların % 18.9'u homozigot MTHFR A1298C taşıyıcısı, hastaların % 17'si heterozigot Faktör V Leiden G1691A taşıyıcısı, hastaların % 43,4'ü 4G / 4G taşıyıcısı, hastaların % 34'ü PAI için 4G / 5G varyasyon taşıyıcısı, hastaların % 22,7'si heterozigot Factor XIII taşıyıcısı, hastaların% 49,1'i ins / del taşıyıcısı ve hastaların% 37,7'si ACE için del / del varyasyon taşıyıcısı idi. Tüm hastalarda, kalıtsal trombofili için homozigot ve / veya bileşik heterozigot varyasyonlardan en az biri vardı.

Sonuç: DS'lu hastalar tromboz ilişkili kardiyovasküler sistem hastalıkları açısından yüksek risk taşımaktadır. Kalıtsal trombofili ile ilişkili komplikasyonları azaltmak için alınacak önlemlerle (tıbbi, sosyal, yaşam tarzı vb. ile ilgili) DS'lu bireylerin ortalama yaşam beklentisinin artırılabileceği söylenebilir.

Keywords

Down Sendromu kalıtsal trombofili protrombotik risk faktörleri

References

  • 1. Mourato FA, Villachan LRR, Mattos SDS. Prevalence and Profile of Congenital Heart Disease and Pulmonary Hypertension in Down Syndrome in a Pediatric Cardiology Service. Rev Paul Pediatr. 2014 Jun;32(2):159-63. doi: 10.1590/0103-0582201432218913.
  • 2. Asim A, Kumar A, Muthuswamy S, Jain S and Agarwal S “Down syndrome: an insight of the disease” Journal of Biomedical Science (2015) 22:41 DOI 10.1186/s12929-015-0138-y
  • 3. Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK. Risk of Major Cardiovascular Events in People with Down Syndrome PLOS ONE | DOI:10.1371/journal.pone.0137093 September 30, 2015
  • 4. Okur M, Eroz R, Bektas MS, Gulsen S, Bahadir A, Turker Y, et al. The Relationship Between Congenital Heart Defects And e-Nos Gene In Down Syndrome. Genet Couns. . 2016;27(3):285-293.
  • 5. Tarlaci S, Sagduyu A. Cerebral venous thrombosis in Down's syndrome. Clin Neurol Neurosurg. 2001 Dec;103(4):242-4. doi: 10.1016/s0303-8467(01)00147-0.
  • 6. Williams MI, Nand S. Superior sagittal sinus thrombosis in a child with Down syndrome. J Paediatr Child Health. 2003 Apr;39(3):226-8. doi: 10.1046/j.1440-1754.2003.00132.x.
  • 7. Gaggero R, Donati PT, Curia R, De Negri M. Occlusion of unilateral carotid artery in Down syndrome. Brain Dev. Jan-Feb 1996;18(1):81-3. doi: 10.1016/0387-7604(95)00114-x.
  • 8. Chiasakul T, Jesus ED, Tong J, Chen Y, Crowther M, Garcia D, et al. Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8: e012877. DOI: 10.1161/JAHA.119.012877.
  • 9. Munshi R, Panchal F, Kulkarni V, and Chaurasia A. Methylenetetrahydrofolate reductase polymorphism in healthy volunteers and its correlation with homocysteine levels in patients with thrombosis. Indian J Pharmacol. 2019 Jul-Aug; 51(4): 248–254.doi: 10.4103/ijp.IJP_215_19
  • 10. Garrido-Barbero M, Arnaez J, Loureiro B, Arca G, Agut T, and Garcia-Alix A. The Role of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Mutations in Neonatal Cerebral Sinovenous Thrombosis. Clinical and Applied Thrombosis/Hemostasis Volume 25: 1-6. DOI: 10.1177/1076029619834352
  • 11. Byrnes JR, and Wolberg AS, Newly-recognized roles of factor XIII in thrombosis. Semin Thromb Hemost. 2016 June ; 42(4): 445–454. doi:10.1055/s-0036-1571343.
  • 12. Liu C, Yang J, Han W, Zhang Q, Shang X, Li X, et al. Polymorphisms in ApoB gene are associated with risk of myocardial infarction and serum ApoB levels in a Chinese population. Int J Clin Exp Med 2015;8(9):16571-16577
  • 13. Xiang Q, Ji SD, Zhang Z, Zhao X, and Cui YM. Identification of ITGA2B and ITGB3 Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function. Biomed Res Int. 2016;2016:5675084. doi: 10.1155/2016/5675084.
  • 14. Herm J, Hoppe B, Siegerink B, Nolte CH, Koscielny J , Haeusler KG. A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients With Ischemic Stroke, Myocardial Infarction, or Peripheral Arterial Occlusive Disease. Front Cardiovasc Med. 2017 Jun 9;4:39. doi: 10.3389/fcvm.2017.00039.
  • 15. Güler A, Şahin MA, Tavlaşoğlu M, Yokuşoğlu M. Atriyal septal defekt, derin ven trombozu, tromboembolizm ve tekrarlayan spontan abortusu olan bir olguda metilentetrahidrofolat redüktaz polimorfizmi. Türk Göğüs Kalp Damar Cerrahisi Dergisi. Eki 2012, Cilt 20, Sayı 4, Sayfalar 907-909
  • 16. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233-70. doi: 10.1093/ehjci/jev014. Review. Erratum in: Eur Heart J Cardiovasc Imaging. 2016 Apr;17(4):412. Eur Heart J Cardiovasc Imaging. 2016 Sep;17 (9):969
  • 17. Petik B, Cevik MO, Sirik M, Colak D and Erturk SM. Disappearing Inferior Vena Cava in A Pediatric Patient with Down Syndrome and Hereditary Thrombophilia. Journal of the Belgian Society of Radiology, 100(1): 22, pp. 1–4, DOI: http://dx.doi.org/10.5334/jbr-btr.975
  • 18. Lupi-Herrera E, Lo ´pez MES, Dimas AJL, Martı ´nez MEN, Gamboa R, Go ´mez CH, et al. Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease. Clin Appl Thromb Hemost. Clin Appl Thromb Hemost. 2019; 25: 1-8. doi: 10.1177/1076029618780344.
  • 19. Kaur A, Kaur A. Maternal MTHFR Polymorphism (677 C-T) and Risk of Down's Syndrome Child: Meta-Analysis. J Genet. 2016 Sep;95(3):505-13. doi: 10.1007/s12041-016-0657-7.
  • 20. Boekholdt SM, Bijsterveld NR, Moons AHM, Levi M, BullerHR, Peters RJG. Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction. Circulation. 2001 Dec 18;104(25):3063-8. doi: 10.1161/hc5001.100793.
  • 21. Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G. The effect of the plasminogen activator inhibitor-14G/5G polymorphism on the thrombotic risk. Thromb Res. 2008;122(6):736-42.doi:10.1016/j.thromres.2007.09.005.
  • 22. Nair V, Yanamandra U, Kumud R, and Ghosh K. PAI-1 polymorphism as a cause of severe high altitude associated arteriovenous thrombosis. BMJ Case Rep. 2016; 2016: bcr2016217361. doi: 10.1136/bcr-2016-217361
  • 23. Hotoleanu C. Genetic Risk Factors in Venous Thromboembolism. Adv. Exp. Med. Biol. 2017;906:253-272. doi: 10.1007/5584_2016_120.
  • 24. Gao LX , Ding QL , Wu KX , Hu J , Wang XF , Dong CL, et al. Correlation of Thrombosis and Prothrombotic State With Coagulation Factor V Gene Polymorphism and APCR. HHcy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1850-1855. doi: 10.7534/j.issn.1009-2137.2016.06.043.
  • 25. Xiang Q, Ji SD, Zhang Z, Zhao X and Cui YM. Identification of ITGA2B and ITGB3 Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function. Biomed Res Int. 2016; 2016: 5675084. doi: 10.1155/2016/5675084
  • 26. Hanscombe KB, Traylor M, Hysi PG, Bevan S, Dichgans M, Rothwell PM, et al. FRCPE; the METASTROKE Consortium; the Wellcome Trust Case Control Consortium 2; Frances M.K. Williams, PhD*; Hugh S. Markus, DM*; Cathryn M. Lewis, PhD* Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke. Stroke. 2015 Aug;46(8):2069-74. doi: 10.1161/STROKEAHA.115.009387.
  • 27. Zhang H, Liu L, Tian J. Molecular mechanisms of congenital heart disease in down syndrome. Volume 6, Issue 4, 2019, Pages 372-377. https://doi.org/10.1016/j.gendis.2019.06.007

Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome

Year 2021, Volume: 13 Issue: 1, 89 - 93, 11.03.2021

İbrahim Halil Damar Recep Eröz Önder Kiliçaslan

https://doi.org/10.18521/ktd.823900
Cited By: 2

Abstract

Objective: Down Syndrome (DS) is defined as chromosome 21 trisomy and associated with cardiovascular system diseases. We aimed to study inherited thrombophilia genes (MTHFR A1298C, MTHFR C677T, Factor II G20210A, Factor V Leiden G1691A, Factor V Cambridge G1091C, Factor XIII, APOB, ITGB3, FVHR2, FGB, PAI-1 and ACE) in patients with DS.

Materials and Methods: A total of 53 patients with DS (32 male and 21 female) were included in the study. Demographical, laboratory and clinical features of cases were recorded. 12-lead Electrocardiogram (ECG), transthoracic echocardiography and the inherited thrombophilia genes were evaluated.

Results: The clinical and developmental defect findings of the patients were high. The 39.6% of patients had both heterozygous MTHFR C677T and heterozygous MTHFR A1298C carriers, the 18.9% of patients had homozygous MTHFR A1298C carriers, the 17% of patients had heterozygous Factor V Leiden G1691A carriers, the 43.4% of patients had 4G/4G carriers, the 34% of patients had 4G/5G variation carriers for PAI, the 22.7% of patients had heterozygous FactorXIII carriers, the 49.1% of patients had ins/del carriers and the 37.7% of patients had del/del variation carriers for ACE. All patients had at least one of the homozygous and/or compound heterozygous variations for the inherited thrombophilia.


Conclusions: The patients with DS have a high risk for thrombosis-related cardiovascular system diseases. It may be said that the average life expectancy of individuals with DS may be increased by precautions (related to medical, social, lifestyle, etc.) to reduce complications associated with hereditary thrombophilia.

Keywords

Down Syndrome inherited thrombophilia prothrombotic risk factors cardiovascular diseases

References

  • 1. Mourato FA, Villachan LRR, Mattos SDS. Prevalence and Profile of Congenital Heart Disease and Pulmonary Hypertension in Down Syndrome in a Pediatric Cardiology Service. Rev Paul Pediatr. 2014 Jun;32(2):159-63. doi: 10.1590/0103-0582201432218913.
  • 2. Asim A, Kumar A, Muthuswamy S, Jain S and Agarwal S “Down syndrome: an insight of the disease” Journal of Biomedical Science (2015) 22:41 DOI 10.1186/s12929-015-0138-y
  • 3. Sobey CG, Judkins CP, Sundararajan V, Phan TG, Drummond GR, Srikanth VK. Risk of Major Cardiovascular Events in People with Down Syndrome PLOS ONE | DOI:10.1371/journal.pone.0137093 September 30, 2015
  • 4. Okur M, Eroz R, Bektas MS, Gulsen S, Bahadir A, Turker Y, et al. The Relationship Between Congenital Heart Defects And e-Nos Gene In Down Syndrome. Genet Couns. . 2016;27(3):285-293.
  • 5. Tarlaci S, Sagduyu A. Cerebral venous thrombosis in Down's syndrome. Clin Neurol Neurosurg. 2001 Dec;103(4):242-4. doi: 10.1016/s0303-8467(01)00147-0.
  • 6. Williams MI, Nand S. Superior sagittal sinus thrombosis in a child with Down syndrome. J Paediatr Child Health. 2003 Apr;39(3):226-8. doi: 10.1046/j.1440-1754.2003.00132.x.
  • 7. Gaggero R, Donati PT, Curia R, De Negri M. Occlusion of unilateral carotid artery in Down syndrome. Brain Dev. Jan-Feb 1996;18(1):81-3. doi: 10.1016/0387-7604(95)00114-x.
  • 8. Chiasakul T, Jesus ED, Tong J, Chen Y, Crowther M, Garcia D, et al. Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis. J Am Heart Assoc. 2019;8: e012877. DOI: 10.1161/JAHA.119.012877.
  • 9. Munshi R, Panchal F, Kulkarni V, and Chaurasia A. Methylenetetrahydrofolate reductase polymorphism in healthy volunteers and its correlation with homocysteine levels in patients with thrombosis. Indian J Pharmacol. 2019 Jul-Aug; 51(4): 248–254.doi: 10.4103/ijp.IJP_215_19
  • 10. Garrido-Barbero M, Arnaez J, Loureiro B, Arca G, Agut T, and Garcia-Alix A. The Role of Factor V Leiden, Prothrombin G20210A, and MTHFR C677T Mutations in Neonatal Cerebral Sinovenous Thrombosis. Clinical and Applied Thrombosis/Hemostasis Volume 25: 1-6. DOI: 10.1177/1076029619834352
  • 11. Byrnes JR, and Wolberg AS, Newly-recognized roles of factor XIII in thrombosis. Semin Thromb Hemost. 2016 June ; 42(4): 445–454. doi:10.1055/s-0036-1571343.
  • 12. Liu C, Yang J, Han W, Zhang Q, Shang X, Li X, et al. Polymorphisms in ApoB gene are associated with risk of myocardial infarction and serum ApoB levels in a Chinese population. Int J Clin Exp Med 2015;8(9):16571-16577
  • 13. Xiang Q, Ji SD, Zhang Z, Zhao X, and Cui YM. Identification of ITGA2B and ITGB3 Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function. Biomed Res Int. 2016;2016:5675084. doi: 10.1155/2016/5675084.
  • 14. Herm J, Hoppe B, Siegerink B, Nolte CH, Koscielny J , Haeusler KG. A Prothrombotic Score Based on Genetic Polymorphisms of the Hemostatic System Differs in Patients With Ischemic Stroke, Myocardial Infarction, or Peripheral Arterial Occlusive Disease. Front Cardiovasc Med. 2017 Jun 9;4:39. doi: 10.3389/fcvm.2017.00039.
  • 15. Güler A, Şahin MA, Tavlaşoğlu M, Yokuşoğlu M. Atriyal septal defekt, derin ven trombozu, tromboembolizm ve tekrarlayan spontan abortusu olan bir olguda metilentetrahidrofolat redüktaz polimorfizmi. Türk Göğüs Kalp Damar Cerrahisi Dergisi. Eki 2012, Cilt 20, Sayı 4, Sayfalar 907-909
  • 16. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging. 2015 Mar;16(3):233-70. doi: 10.1093/ehjci/jev014. Review. Erratum in: Eur Heart J Cardiovasc Imaging. 2016 Apr;17(4):412. Eur Heart J Cardiovasc Imaging. 2016 Sep;17 (9):969
  • 17. Petik B, Cevik MO, Sirik M, Colak D and Erturk SM. Disappearing Inferior Vena Cava in A Pediatric Patient with Down Syndrome and Hereditary Thrombophilia. Journal of the Belgian Society of Radiology, 100(1): 22, pp. 1–4, DOI: http://dx.doi.org/10.5334/jbr-btr.975
  • 18. Lupi-Herrera E, Lo ´pez MES, Dimas AJL, Martı ´nez MEN, Gamboa R, Go ´mez CH, et al. Polymorphisms C677T and A1298C of MTHFR Gene: Homocysteine Levels and Prothrombotic Biomarkers in Coronary and Pulmonary Thromboembolic Disease. Clin Appl Thromb Hemost. Clin Appl Thromb Hemost. 2019; 25: 1-8. doi: 10.1177/1076029618780344.
  • 19. Kaur A, Kaur A. Maternal MTHFR Polymorphism (677 C-T) and Risk of Down's Syndrome Child: Meta-Analysis. J Genet. 2016 Sep;95(3):505-13. doi: 10.1007/s12041-016-0657-7.
  • 20. Boekholdt SM, Bijsterveld NR, Moons AHM, Levi M, BullerHR, Peters RJG. Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction. Circulation. 2001 Dec 18;104(25):3063-8. doi: 10.1161/hc5001.100793.
  • 21. Tsantes AE, Nikolopoulos GK, Bagos PG, Bonovas S, Kopterides P, Vaiopoulos G. The effect of the plasminogen activator inhibitor-14G/5G polymorphism on the thrombotic risk. Thromb Res. 2008;122(6):736-42.doi:10.1016/j.thromres.2007.09.005.
  • 22. Nair V, Yanamandra U, Kumud R, and Ghosh K. PAI-1 polymorphism as a cause of severe high altitude associated arteriovenous thrombosis. BMJ Case Rep. 2016; 2016: bcr2016217361. doi: 10.1136/bcr-2016-217361
  • 23. Hotoleanu C. Genetic Risk Factors in Venous Thromboembolism. Adv. Exp. Med. Biol. 2017;906:253-272. doi: 10.1007/5584_2016_120.
  • 24. Gao LX , Ding QL , Wu KX , Hu J , Wang XF , Dong CL, et al. Correlation of Thrombosis and Prothrombotic State With Coagulation Factor V Gene Polymorphism and APCR. HHcy. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2016 Dec;24(6):1850-1855. doi: 10.7534/j.issn.1009-2137.2016.06.043.
  • 25. Xiang Q, Ji SD, Zhang Z, Zhao X and Cui YM. Identification of ITGA2B and ITGB3 Single-Nucleotide Polymorphisms and Their Influences on the Platelet Function. Biomed Res Int. 2016; 2016: 5675084. doi: 10.1155/2016/5675084
  • 26. Hanscombe KB, Traylor M, Hysi PG, Bevan S, Dichgans M, Rothwell PM, et al. FRCPE; the METASTROKE Consortium; the Wellcome Trust Case Control Consortium 2; Frances M.K. Williams, PhD*; Hugh S. Markus, DM*; Cathryn M. Lewis, PhD* Genetic Factors Influencing Coagulation Factor XIII B-Subunit Contribute to Risk of Ischemic Stroke. Stroke. 2015 Aug;46(8):2069-74. doi: 10.1161/STROKEAHA.115.009387.
  • 27. Zhang H, Liu L, Tian J. Molecular mechanisms of congenital heart disease in down syndrome. Volume 6, Issue 4, 2019, Pages 372-377. https://doi.org/10.1016/j.gendis.2019.06.007
There are 27 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Articles
Authors

İbrahim Halil Damar 0000-0001-6420-0122

Recep Eröz 0000-0003-0840-2613

Önder Kiliçaslan 0000-0002-9311-006X

Publication Date March 11, 2021
Acceptance Date January 29, 2021
Published in Issue Year 2021 Volume: 13 Issue: 1

Cite

APA Damar, İ. H., Eröz, R., & Kiliçaslan, Ö. (2021). Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal, 13(1), 89-93. https://doi.org/10.18521/ktd.823900
AMA Damar İH, Eröz R, Kiliçaslan Ö. Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal. March 2021;13(1):89-93. doi:10.18521/ktd.823900
Chicago Damar, İbrahim Halil, Recep Eröz, and Önder Kiliçaslan. “Frequency of Hereditary Prothrombotic Risk Factors in Patients With Down Syndrome”. Konuralp Medical Journal 13, no. 1 (March 2021): 89-93. https://doi.org/10.18521/ktd.823900.
EndNote Damar İH, Eröz R, Kiliçaslan Ö (March 1, 2021) Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal 13 1 89–93.
IEEE İ. H. Damar, R. Eröz, and Ö. Kiliçaslan, “Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome”, Konuralp Medical Journal, vol. 13, no. 1, pp. 89–93, 2021, doi: 10.18521/ktd.823900.
ISNAD Damar, İbrahim Halil et al. “Frequency of Hereditary Prothrombotic Risk Factors in Patients With Down Syndrome”. Konuralp Medical Journal 13/1 (March 2021), 89-93. https://doi.org/10.18521/ktd.823900.
JAMA Damar İH, Eröz R, Kiliçaslan Ö. Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal. 2021;13:89–93.
MLA Damar, İbrahim Halil et al. “Frequency of Hereditary Prothrombotic Risk Factors in Patients With Down Syndrome”. Konuralp Medical Journal, vol. 13, no. 1, 2021, pp. 89-93, doi:10.18521/ktd.823900.
Vancouver Damar İH, Eröz R, Kiliçaslan Ö. Frequency of hereditary prothrombotic risk factors in patients with Down Syndrome. Konuralp Medical Journal. 2021;13(1):89-93.

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