E-ISSN: 2619-9467

Contents    Cover    Publication Date: 19 Apr 2024
Year 2024 - Volume 34 - Issue 1

Open Access

Peer Reviewed

223 Viewed314 Downloaded

Host Genetic Polymorphisms and Disease Severity in Pregnant Women with COVID-19 in Türkiye

Full Text PDF  
JCOG. 2024;34(1):1-9
DOI: 10.5336/jcog.2023-96185
Article Language: EN
Copyright Ⓒ 2020 by Türkiye Klinikleri. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Objective: The study aimed to analyze the association between coronavirus disease-2019 (COVID-19) disease severity and genetic susceptibility in pregnant women. Material and Methods: The research included 54 pregnant women with confirmed COVID-19 diagnosis. All volunteers were evaluated physically and biochemically. Angiotensin-converting enzyme (ACE)2 (p.T27A A>G, p.G326E G>A, p.K419T A>C, ACE (p.T776T A>G, and g.16471_16472delinsALU (I/D), AGTR1 c.*86A>C, methylenetetrahydrofolate-reductase (MTHFR) p.A222V C>T and PAI-1-844 G>A were analyzed. Results: The allele frequency was also compared with control groups of the different studies made on Turkish women. MTHFR ''CT'' genotype compared to ''CC'' had lower platelet counts (p=0.015). In ACE ''ID'' genotype, there was a lower D-dimer level compared to ''DD'' genotype (p=0.02). In PAI-1-844G>A, the AA vs. AG+GG genotype and AA vs. GG genotype elevate the risk of hospitalization 6.4-fold (OR: 6.4 95% (Cl): 1.6-25.8 p=0.009), and 4.6-fold (OR: 4.6 95% CI:1.0-21.6 p=0.049), respectively. In MTHFR p.A222V, to have CC vs. CT genotype increased the risk of enoxaparin and antibiotic use 4.1-fold and 3.2-fold at the borderline significance (OR: 4.1 95% Cl: 0.99-16.9 p=0.052 and OR: 3.2 95% Cl: 0.98-10.5 p=0.053), respectively. An allele frequency difference wasn't found between the patient and the healthy women related to the investigated polymorphisms. Conclusion: PAI-1-844G>A, MTHFR p.A222V, and ACE (I/D) associated with a poor COVID-19 outcome, the risk of enoxaparin and antibiotic use, and also increased risk of hospitalization. Allele frequencies of the genes were not different between healthy control women and women with COVID-19; genetic variation may not influence the risk of infection but disease severity.
  1. Figliozzi S, Masci PG, Ahmadi N, Tondi L, Koutli E, Aimo A, et al. Predictors of adverse prognosis in COVID-19: a systematic review and meta-analysis. Eur J Clin Invest. 2020;50(10):e13362. [Crossref]  [PubMed] 
  2. Benhamou D, Keita H, Ducloy-Bouthors AS; Obstetric Anaesthesia and Critical Care Club Working Group. Coagulation changes and thromboembolic risk in COVID-19 obstetric patients. Anaesth Crit Care Pain Med. 2020;39(3):351-3. [Crossref]  [PubMed]  [PMC] 
  3. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10(1):111-3. [Crossref]  [PubMed] 
  4. Torres-Carrillo NM, Torres-Carrillo N, Vázquez-Del Mercado M, Delgado-Rizo V, Oregón-Romero E, Parra-Rojas I, et al. The -844 G/A PAI-1 polymorphism is associated with mRNA expression in rheumatoid arthritis. Rheumatol Int. 2008;28(4):355-60. [Crossref]  [PubMed] 
  5. Suryamohan K, Diwanji D, Stawiski EW, Gupta R, Miersch S, Liu J, et al. Human ACE2 receptor polymorphisms and altered susceptibility to SARS-CoV-2. Commun Biol. 2021;4(1):475. [Crossref]  [PubMed]  [PMC] 
  6. Qi F, Qian S, Zhang S, Zhang Z. Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses. Biochem Biophys Res Commun. 2020;526(1):135-40. [Crossref]  [PubMed]  [PMC] 
  7. Raghav PK, Raghav A, Lathwal A, Saxena A, Mann Z, Sengar M, et al. Experimental and clinical data analysis for identification of COVID-19 resistant ACE2 mutations. Sci Rep. 2023;13(1):2351. [Crossref]  [PubMed]  [PMC] 
  8. Abboud N, Ghazouani L, Saidi S, Ben-Hadj-Khalifa S, Addad F, Almawi WY, et al. Association of PAI-1 4G/5G and -844G/A gene polymorphisms and changes in PAI-1/tissue plasminogen activator levels in myocardial infarction: a case-control study. Genet Test Mol Biomarkers. 2010;14(1):23-7. [Crossref]  [PubMed] 
  9. Rigat B, Hubert C, Corvol P, Soubrier F. PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1). Nucleic Acids Res. 1992;20(6):1433. [Crossref]  [PubMed]  [PMC] 
  10. Herrera CL, Castillo W, Estrada P, Mancilla B, Reyes G, Saavedra N, et al. Association of polymorphisms within the Renin-Angiotensin System with metabolic syndrome in a cohort of Chilean subjects. Arch Endocrinol Metab. 2016;60(3):190-8. [Crossref]  [PubMed]  [PMC] 
  11. Ghafil FA, Mohammad BI, Al-Janabi HS, Hadi NR, Al-Aubaidy HA. Genetic polymorphism of angiotensin converting enzyme and angiotensin II type 1 receptors and their impact on the outcome of acute coronary syndrome. Genomics. 2020;112(1):867-72. [Crossref]  [PubMed] 
  12. Polat S, Şimşek Y. MTHFR C677T polymorphism in Turkish women with polycystic ovary syndrome. Turkish Journal of Endocrinology and Metabolism. 2021;25(1):102-12. [Crossref] 
  13. Dubey P, Reddy SY, Manuel S, Dwivedi AK. Maternal and neonatal characteristics and outcomes among COVID-19 infected women: an updated systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020;252:490-501. [Crossref]  [PubMed]  [PMC] 
  14. Zambrano LD, Ellington S, Strid P, Galang RR, Oduyebo T, Tong VT, et al; CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team. Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status - United States, January 22-October 3, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(44):1641-7. [Crossref]  [PubMed]  [PMC] 
  15. Zuo Y, Warnock M, Harbaugh A, Yalavarthi S, Gockman K, Zuo M, et al. Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients. Sci Rep. 2021;11(1):1580. [Crossref]  [PubMed]  [PMC] 
  16. Polat S, Şimşek Y. Plasminogen activator inhibitor-1 polymorphism and risk of polycystic ovary syndrome in Turkish women. Meta Gene. 2021;30:100959. [Crossref] 
  17. Balint B, Jepchumba VK, Guéant JL, Guéant-Rodriguez RM. Mechanisms of homocysteine-induced damage to the endothelial, medial and adventitial layers of the arterial wall. Biochimie. 2020;173:100-6. [Crossref]  [PubMed] 
  18. Zoccolella S, Martino D, Defazio G, Lamberti P, Livrea P. Hyperhomocysteinemia in movement disorders: current evidence and hypotheses. Curr Vasc Pharmacol. 2006;4(3):237-43. [Crossref]  [PubMed] 
  19. Ponti G, Pastorino L, Manfredini M, Ozben T, Oliva G, Kaleci S, et al. COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase (MTHFR) gene prevalence. J Clin Lab Anal. 2021;35(7):e23798. [Crossref]  [PubMed]  [PMC] 
  20. Tekcan A, Cihangiroglu M, Capraz M, Capraz A, Yigit S, Nursal AF, et al. Association of ACE ID, MTHFR C677T, and MIF-173GC variants with the clinical course of COVID-19 patients. Nucleosides Nucleotides Nucleic Acids. 2023;42(10):782-96. [Crossref]  [PubMed] 
  21. McCully KS. Homocysteine and the pathogenesis of atherosclerosis. Expert Rev Clin Pharmacol. 2015;8(2):211-9. [Crossref]  [PubMed] 
  22. Naghshtabrizi B, Shakerian F, Hajilooi M, Emami F. Plasma homocysteine level and its genotypes as a risk factor for coronary artery disease in patients undergoing coronary angiography. J Cardiovasc Dis Res. 2012;3(4):276-9. [Crossref]  [PubMed]  [PMC] 
  23. Rongioletti M, Baldassini M, Papa F, Capoluongo E, Rocca B, Cristofaro RD, et al. Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase. Platelets. 2005;16(3-4):185-90. [Crossref]  [PubMed] 
  24. Karadeniz M, Erdogan M, Zengi A, Eroglu Z, Tamsel S, Olukman M, et al. Methylenetetrahydrofolate reductase C677T gene polymorphism in Turkish patients with polycystic ovary syndrome. Endocrine. 2010;38(1):127-33. [Crossref]  [PubMed] 
  25. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86(4):1343-6. [Crossref]  [PubMed]  [PMC] 
  26. de Carvalho SS, Simões e Silva AC, Sabino Ade P, Evangelista FC, Gomes KB, Dusse LM, et al. Influence of ACE I/D Polymorphism on circulating levels of plasminogen activator inhibitor 1, D-dimer, ultrasensitive C-reactive protein and transforming growth factor β1 in patients undergoing hemodialysis. PLoS One. 2016;11(3):e0150613. [Crossref]  [PubMed]  [PMC] 
  27. Zhang L, Yan X, Fan Q, Liu H, Liu X, Liu Z, et al. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemost. 2020;18(6):1324-9. [Crossref]  [PubMed]  [PMC] 
  28. İnanir S, Yiğit S, Çam Çelikel F, Ates O, Taycan SE, Nursal AF, et al. Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population. Archives of Clinical Psychiatry. 2016;43(2):27-30. [Link] 
  29. Bayram B, Kılıççı C, Onlü H, Ozkurt M, Erkasap N, Yıldırım E, et al. Association of angiotensin converting enzyme (ACE) gene I/D polymorphism and polycystic ovary syndrome (PCOS). Gene. 2011;489(2):86-8. [Crossref]  [PubMed] 
  30. Alkanli N, Sipahi T, Okman Kilic T, Sener S. Lack of association between ACE I/D and AGTR1 A1166C Gene polymorphisms and preeclampsia in Turkish pregnant women of Trakya region. Journal of Gynecology and Obstetrics. 2014;2(4):49-53. [Crossref] 
  31. Cao Y, Sun Y, Tian X, Bai Z, Gong Y, Qi J, et al. Analysis of ACE2 gene-encoded proteins across mammalian species. Front Vet Sci. 2020;7:457. [Crossref]  [PubMed]  [PMC] 
  32. Turner AJ, Tipnis SR, Guy JL, Rice G, Hooper NM. ACEH/ACE2 is a novel mammalian metallocarboxypeptidase and a homologue of angiotensin-converting enzyme insensitive to ACE inhibitors. Can J Physiol Pharmacol. 2002;80(4):346-53. [Crossref]  [PubMed] 
  33. van Geel PP, Pinto YM, Voors AA, Buikema H, Oosterga M, Crijns HJ, et al. Angiotensin II type 1 receptor A1166C gene polymorphism is associated with an increased response to angiotensin II in human arteries. Hypertension. 2000;35(3):717-21. [Crossref]  [PubMed] 
  34. Peng N, Liu JT, Gao DF, Lin R, Li R. Angiotensin II-induced C-reactive protein generation: inflammatory role of vascular smooth muscle cells in atherosclerosis. Atherosclerosis. 2007;193(2):292-8. [Crossref]  [PubMed] 
  35. Wang CH, Li SH, Weisel RD, Fedak PW, Dumont AS, Szmitko P, et al. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation. 2003;107(13):1783-90. [Crossref]  [PubMed] 
  36. Bahramali E, Firouzabadi N, Jonaidi-Jafari N, Shafiei M. Renin-angiotensin system genetic polymorphisms: lack of association with CRP levels in patients with coronary artery disease. J Renin Angiotensin Aldosterone Syst. 2014;15(4):559-65. [Crossref]  [PubMed] 
  37. Gormez S, Ekicibasi E, Degirmencioglu A, Paudel A, Erdim R, Gumusel HK, et al. Association between renin-angiotensin-aldosterone system inhibitor treatment, neutrophil-lymphocyte ratio, D-Dimer and clinical severity of COVID-19 in hospitalized patients: a multicenter, observational study. J Hum Hypertens. 2021;35(7):588-97. [Crossref]  [PubMed]  [PMC]