Study of the impact of the ACE1 I/D polymorphism and SARS-COV-2 Ct value on COVID-19 infection
Bioquímica y Patología Clínica (ByPC)
pdf (Spanish)
html (Spanish)

Keywords

COVID-19
Ct value
ACE1 polymorphism
symptoms
genetic susceptibility

How to Cite

Study of the impact of the ACE1 I/D polymorphism and SARS-COV-2 Ct value on COVID-19 infection. (2023). Biochemistry and Clinical Pathology Journal, 87(1), 35-39. https://doi.org/10.62073/bypc.v87i1.239

Abstract

The Angiotensin Converting Enzyme (ACE1) gene presents an insertion/deletion (I/D) polymorphism(rs4646994). The deletion has been associated with a lower expression of ACE2, the SARS-Cov-2 receptor. It has been described that the SARS-Cov-2 cycle threshold (Ct) value is related to the development of symptoms. Our objective was to evaluate whether the rs4646994 polymorphism is linked to the susceptibility to SARSCov- 2 infection and whether the Ct value influences the development of symptoms. We studied 658 unrelated individuals: 325 uninfected individuals, 132 asymptomatic carriers and 201 symptomatic individuals, in whom the presence/absence of SARS-Cov-2 in a nasopharyngeal swab sample was determined using a commercial RT-qPCR kit. The age, gender, Ct value, and symptoms of each individual were recorded. Samples were genotyped by PCR for rs4646994. No differences were found in the age and gender of SARS-Cov-2-positive patients, or in the presence of symptoms. Significant differences were found between the presence of symptoms and the Ct value (asymptomatic Ct: 23.84 vs symptomatic Ct: 20.22, p <0.001). Significant differences were found between the presence of general malaise, fever, headache, odynophagia, cough, myalgia and anosmia and the Ct value (p <0.001). The D allele frequency in uninfected individuals was 0.51, whereas that in asymptomatic carriers was 0.54 and that in symptomatic ones was 0.53, showing no significant differences between the three groups. Our results suggest that the rs4646994 polymorphism is not linked to the susceptibility to SARSCov- 2 infection in our population, and that the viral load, analyzed as the Ct value, influences the appearance of some symptoms.

pdf (Spanish)
html (Spanish)

References

Chan JF-W, Yuan S, Kok K-H, Kelvin K, Hin C, Jin Y et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395: 514-23.

https://doi.org/10.1016/S0140-6736(20)30154-9

Weekly epidemiological update on COVID-19 - Edition 80 [Consultado 2022 27 Feb]. Disponible en: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---22-february-2022. 3. Coronavirus disease (COVID-19) [Consultado 2022 27 Feb]. Disponible en: https://www.who.int/health-topics/coronavirus#tab=tab_3

The COVID-19 Host Genetics Initiative. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-Cov-2 virus pandemic. Eur J Hum Genet 2020;28:715-718. https://doi.org/10.1038/s41431-020-0636-6

Fakhroo AD, Al Thani AA, Yassine HM. Markers Associated with COVID-19 Susceptibility, Resistance, and Severity. Viruses 2021; 13: 45. https://doi.org/10.3390/v13010045

Tracking SARS-CoV-2 variants [Consultado 2022 27 Feb]. Disponible en https://www.who.int/en/activities/tracking-SARS-Cov-2-variants/

He X, Lau E H Y, Wu P, Deng X, Wang J, Hao X, et al. Temporal dynamics in viral shedding and transmissibility of COVID-19. Nat. Med.2020; 26: 672-675. https://doi.org/10.1038/s41591-020-0869-5

Cevik M, Tate M, Ollie LO, Maraolo AE, Schafers J, Ho A. SARS-CoV, and MERSCoV viral load dynamics, duration of viral shedding, and infectiousness: A systematic review and meta-analysis. Lancet Microbe 2 2021; e13-e22.

https://doi.org/10.1016/S2666-5247(20)30172-5

Liu Y, Yan LM, Wan L, Xiang TX, Le A, Liu JM et al. Viral dynamics in mild and severe cases of COVID-19. Lancet Infect. 2020; 20: 656-657. https://doi.org/10.1016/S1473-3099(20)30232-2

Cascella M, Rajnik M, Aleem A, Dulebohn S C, Di Napoli Features R. Evaluation and Treatment Coronavirus (COVID-19). 2021 StatPearls [Consultado 2022 27 Feb]. Disponible en https://www.ncbi.nlm.nih.gov/books/NBK554776/ 11. 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; 86:1343. https://doi.org/10.1172/JCI114844

Li M, Schifanella L, Larsen P A. Alu retrotransposons and COVID-19 susceptibility and morbidity. Human Genomics, 2021;15(2):1-11. https://doi.org/10.1186/s40246-020-00299-9

Aladag E, Tas Z, Ozdemir B S, Akbaba T H, Meltem Akpınar M G, Goker H et al. N. "Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19". JRAAS, 2021; 5509280: 1-7. https://doi.org/10.1155/2021/5509280

Yamamoto N, Ariumi Y, Nishida N, Yamamoto R, Bauer G, Gojobori T et al. SARS-Cov-2 infections and COVID-19 mortalities strongly correlate with ACE1 I/D genotype Gene. 2020 ;758:144944.

https://doi.org/10.1016/j.gene.2020.144944

Delanghe J R, Speeckaert M M, De Buyzere M L. COVID-19 infections are also affected by human ACE1 D/I polymorphism. Clin Chem Lab Med. 2020 ;58(7):1125-1126. https://doi.org/10.1515/cclm-2020-0425

Pati A, Manhto HS, Padhi S, Panda, A K. ACE deletion allele is associated with susceptibility to SARS-Cov-2 infection and mortality rate: An epidemiological study in the Asian population. Clin Chim Acta. 2020;510:455-458.

https://doi.org/10.1016/j.cca.2020.08.008

Gómez J, Albaiceta G M, García-Clemente M, López-Larrea C, Amado-Rodríguez L, Lopez-Alonso I et al. Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome. Gene. 2020; 762: 145102.

https://doi.org/10.1016/j.gene.2020.145102

Saadat M. No significant correlation between ACE Ins/Del genetic polymorphism and COVID-19 infection. CCLM 2020; 58(7):1127-1128. https://doi.org/10.1515/cclm-2020-0577

Zuin M, Gentili V, Cervellati C, Rizzo, Zuliani G. Viral Load Difference between Symptomatic and Asymptomatic COVID-19 Patients: Systematic Review and Meta-Analysis. Infect. Dis. Rep. 2021; 13:645-653.

https://doi.org/10.3390/idr13030061

Arons M M, Hatfield K M, Reddy S C. Presymptomatic SARS-Cov-2 infections and transmission in a skilled nursing facility. N Engl J Med. 2020; 382:2081-2090. https://doi.org/10.1056/NEJMoa2008457

Kimball A, Hatfield K M, Arons M, Allison J, Joanne T, Kevin S et al. Asymptomatic and presymptomatic SARS-Cov-2 infections in residents of a longterm care skilled nursing facility - King County, Washington. MMWR Morb Mortal Wkly Rep. 2020; 69(13):377-381. https://doi.org/10.15585/mmwr.mm6913e1

Salvatore P P, Dawson P, Wadhwa A, Rabold E M, Buono S, Dietrich E A et al. Epidemiological Correlates of Polymerase Chain Reaction Cycle Threshold Values in the Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2). Clin Infect Dis. 2021 ;72(11):e761-e767. https://doi.org/10.1093/cid/ciaa1469

Cho R H W, To Z W H, Yeung Z W C, Tso E Y K, Fung K S C, Chau S K Y et al. COVID-19 Viral Load in the Severity of and Recovery from Olfactory and Gustatory Dysfunction. Laryngoscope. 2020;130(11):2680-2685.

https://doi.org/10.1002/lary.29056

Buchan B W J S, Gmehlin C G, Perez A, Faron M L, Munoz-Price L S, Ledeboer N A. Distribution of SARS-Cov-2 PCR Cycle Threshold Values Provide Practical Insight Into Overall and Target-Specific Sensitivity Among Symptomatic Patients. Am J Clin Pathol . 2020 ;154(4):479-485. https://doi.org/10.1093/ajcp/aqaa133

Euser S, Aronson S, Manders I, Van Lelyveld S, Herpers B, Sinnige J, et al. SARS-Cov-2 viral-load distribution reveals that viral loads increase with age: a retrospective cross-sectional cohort study. Int J Epidemiol. 2021;50(6):1795-1803. https://doi.org/10.1093/ije/dyab145

Lo Presti M, Beck D B, Duggal P, Cummings D A T, Solomon B D. The Role of Host Genetic Factors in Coronavirus Susceptibility: Review of Animal and Systematic Review of Human Literature. AJHG. 2020;107:381-402.

https://doi.org/10.1016/j.ajhg.2020.08.007

Schurr T G. Host genetic factors and susceptibility to SARS-Cov-2 infection Am J Hum Biol. 2020;32(5):e23497.

https://doi.org/10.1002/ajhb.23497

Ballone M S L. ACE polymorphisms and COVID-19-related mortality in Europe. J Mol Med (Berl). 2020;98(11):1505-1509. https://doi.org/10.1007/s00109-020-01981-0