Research Article
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Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population

Year 2024, Volume: 41 Issue: 3, 479 - 484, 30.09.2024

Abstract

Coronavirus disease 2019 (COVID-19) manifests in a wide range of degrees of severity, ranging from asymptomatic to critical disease with high risk of mortality. Gene polymorphism has been found to be associated with severe COVID-19 in different populations around the world. Human Leukocyte Antigen (HLA)‐DRB1*09:01, in particular, has appeared to be more significantly associated with severe COVID‐19 compared to pre-existing comorbidities in a study involving an Asian population. This study investigated HLA‐DRB1*09:01 polymorphism in Indonesian patients who were hospitalized in Sebelas Maret University Hospital with COVID-19 from October 2021 to October 2022 and analyzed whether there is an association with severe COVID-19. Of 154 subjects in total, 102 were non-severe and 52 were severe. We reviewed four single nucleotide polymorphisms (SNP) of HLA-DRB1*09:01, namely rs75314265, rs79572840, rs117501019, and rs11708573. The SNP rs 79572840 population was entirely heterozygote (100%) in both non-severe and severe groups. In both severity groups, SNP rs75314265 was dominated by heterozygote alleles, while rs117501019 and rs11708573 were dominated by homozygote alleles. None of the SNPs were significantly associated with severe COVID-19. Subject characteristics associated with severity were of older age, having comorbidities and higher neutrophil to lymphocyte ratio (p=0.010, 0.030, 0.001, respectively), which potentially confounded the effect of HLA polymorphisms on COVID-19 severity in this study. Gene polymorphism among different populations is a natural phenomenon, hence different studies may yield different conclusions about HLA’s association with COVID-19 severity. Further studies involving more cases over various populations may allow better understanding of genetic markers linked to disease outcomes and prognosis.

Ethical Statement

This study has obtained ethical approval from Ethical Committee of Sebelas Maret University under the reference number 46/UN27.06.6.1/KEP/EC/2021.

Supporting Institution

Sebelas Maret University, Surakarta, Indonesia as provider of funding through research grant

Thanks

None to declare

References

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  • Ishak A, Mehendale M, AlRawashdeh MM, Sestacovschi C, Sharath M, Pandav K, et al. The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature. Gene. 2022 Aug 20;836:146674.
  • Yıldırım M, Arslan G. A moderated mediation effect of stress-related growth and meaning in life in the association between Coronavirus suffering and satisfaction with life: Development of the stress-related growth measure. Front Psychol. 2021 Mar 16;12:648236.
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  • Toyoshima Y, Nemoto K, Matsumoto S, Nakamura Y, Kiyotani K. SARS-CoV-2 genomic variations associated with mortality rate of COVID-19. J Hum Genet. 2020 Dec;65(12):1075-82.
  • Gutiérrez-Bautista JF, Rodriguez-Nicolas A, Rosales-Castillo A, López-Ruz MÁ, Martín-Casares AM, Fernández-Rubiales A, et al. Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients. J Microbiol Immunol Infect. 2022 Jun;55(3):421-7.
  • Ben Shachar S, Barda N, Manor S, Israeli S, Dagan N, Carmi S, et al. MHC Haplotyping of SARS-CoV-2 Patients: HLA Subtypes Are Not Associated with the Presence and Severity of COVID-19 in the Israeli Population. J Clin Immunol. 2021 Aug;41(6):1154-61.
  • Naemi FMA, Al-Adwani S, Al-Khatabi H, Al-Nazawi A. Association between the HLA genotype and the severity of COVID-19 infection among South Asians. J Med Virol. 2021 Jul;93(7):4430-7.
  • Anzurez A, Naka I, Miki S, Nakayama-Hosoya K, Isshiki M, Watanabe Y, et al. Association of HLA-DRB1*09:01 with severe COVID-19. HLA. 2021 Jul;98(1):37-42.
  • Migliorini F, Torsiello E, Spiezia F, Oliva F, Tingart M, Maffulli N. Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature. Eur J Med Res. 2021 Aug 3;26(1):84.
  • Kulski JK, Shiina T, Dijkstra JM. Genomic diversity of the major histocompatibility complex in health and disease. Cells. 2019 Oct 17;8(10):1270.
  • Fakhkhari M, Caidi H, Sadki K. HLA alleles associated with COVID-19 susceptibility and severity in different populations: a systematic review. Egypt J Med Hum Genet. 2023;24(1):10.
  • Dieter C, Brondani LA, Leitão CB, Gerchman F, Lemos NE, Crispim D. Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLoS One. 2022 Jul 6;17(7):e0270627.
  • Liu Q, Wu S, Xue M, Sandford AJ, Wu J, Wang Y, et al. Heterozygote advantage of the rs3794624 polymorphism in CYBA for resistance to tuberculosis in two chinese populations. Sci Rep. 2016 Nov 30;6:38213
  • Taefehshokr N, Taefehshokr S, Hemmat N, Heit B. Covid-19: Perspectives on innate immune evasion. Front Immunol. 2020 Sep 30;11:580641.
  • Mohan AA, Olson LB, Naqvi IA, Morrison SA, Kraft BD, Chen L, et al. Age and comorbidities predict COVID-19 outcome, regardless of innate immune response severity: A single institutional cohort atudy. Crit Care Explor. 2022 Dec 5;4(12):e0799.
  • Toori KU, Qureshi MA, Chaudhry A, Safdar MF. Neutrophil to lymphocyte ratio (NLR) in COVID-19: A cheap prognostic marker in a resource constraint setting. Pak J Med Sci. 2021 Sep-Oct;37(5):1435-9.
  • Russell CD, Lone NI, Baillie JK. Comorbidities, multimorbidity and COVID-19. Nat Med. 2023 Feb;29(2):334-43.
Year 2024, Volume: 41 Issue: 3, 479 - 484, 30.09.2024

Abstract

References

  • Richards F, Kodjamanova P, Chen X, Li N, Atanasov P, Bennetts L, et al. Economic burden of COVID-19: a systematic review. Clinicoecon Outcomes Res. 2022 Apr 28;14:293-307.
  • Setiadi W, Rozi IE, Safari D, Daningrat WO, Johar E, Yohan B, et al. Prevalence and epidemiological characteristics of COVID-19 after one year of pandemic in Jakarta and neighbouring areas, Indonesia: A single center study. PLOS ONE [Internet]. 2022 May 12 [cited 2023 Oct 31];17(5):e0268241. Available from: https://doi.org/10.1371/journal.pone.0268241.
  • Martono, Fatmawati F, Mulyanti S. Risk factors associated with the severity of COVID-19. Malays J Med Sci. 2023 Jun;30(3):84-92.
  • Ishak A, Mehendale M, AlRawashdeh MM, Sestacovschi C, Sharath M, Pandav K, et al. The association of COVID-19 severity and susceptibility and genetic risk factors: A systematic review of the literature. Gene. 2022 Aug 20;836:146674.
  • Yıldırım M, Arslan G. A moderated mediation effect of stress-related growth and meaning in life in the association between Coronavirus suffering and satisfaction with life: Development of the stress-related growth measure. Front Psychol. 2021 Mar 16;12:648236.
  • Williams TM. Human leukocyte antigen gene polymorphism and the histocompatibility laboratory. J Mol Diagn. 2001 Aug;3(3):98-104.
  • Copley HC, Gragert L, Leach AR, Kosmoliaptsis V. Influence of HLA class II polymorphism on predicted cellular immunity against SARS-CoV-2 at the population and individual level. Front Immunol. 2021 Jul 19;12:669357.
  • Kakodkar P, Kaka N, Baig MN. A comprehensive literature review on the clinical presentation, and management of the pandemic Coronavirus Disease 2019 (COVID-19). Cureus. 2020 Apr 6;12(4):e7560.
  • Fakhkhari M, Caidi H, Sadki K. HLA alleles associated with COVID-19 susceptibility and severity in different populations: a systematic review. Egypt J Med Hum Genet. 2023;24(1):10.
  • Wang F, Huang S, Gao R, Zhou Y, Lai C, Li Z, et al. Initial whole-genome sequencing and analysis of the host genetic contribution to COVID-19 severity and susceptibility. Cell Discov. 2020 Nov 10;6(1):83.
  • Toyoshima Y, Nemoto K, Matsumoto S, Nakamura Y, Kiyotani K. SARS-CoV-2 genomic variations associated with mortality rate of COVID-19. J Hum Genet. 2020 Dec;65(12):1075-82.
  • Gutiérrez-Bautista JF, Rodriguez-Nicolas A, Rosales-Castillo A, López-Ruz MÁ, Martín-Casares AM, Fernández-Rubiales A, et al. Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients. J Microbiol Immunol Infect. 2022 Jun;55(3):421-7.
  • Ben Shachar S, Barda N, Manor S, Israeli S, Dagan N, Carmi S, et al. MHC Haplotyping of SARS-CoV-2 Patients: HLA Subtypes Are Not Associated with the Presence and Severity of COVID-19 in the Israeli Population. J Clin Immunol. 2021 Aug;41(6):1154-61.
  • Naemi FMA, Al-Adwani S, Al-Khatabi H, Al-Nazawi A. Association between the HLA genotype and the severity of COVID-19 infection among South Asians. J Med Virol. 2021 Jul;93(7):4430-7.
  • Anzurez A, Naka I, Miki S, Nakayama-Hosoya K, Isshiki M, Watanabe Y, et al. Association of HLA-DRB1*09:01 with severe COVID-19. HLA. 2021 Jul;98(1):37-42.
  • Migliorini F, Torsiello E, Spiezia F, Oliva F, Tingart M, Maffulli N. Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature. Eur J Med Res. 2021 Aug 3;26(1):84.
  • Kulski JK, Shiina T, Dijkstra JM. Genomic diversity of the major histocompatibility complex in health and disease. Cells. 2019 Oct 17;8(10):1270.
  • Fakhkhari M, Caidi H, Sadki K. HLA alleles associated with COVID-19 susceptibility and severity in different populations: a systematic review. Egypt J Med Hum Genet. 2023;24(1):10.
  • Dieter C, Brondani LA, Leitão CB, Gerchman F, Lemos NE, Crispim D. Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: A systematic review and meta-analysis. PLoS One. 2022 Jul 6;17(7):e0270627.
  • Liu Q, Wu S, Xue M, Sandford AJ, Wu J, Wang Y, et al. Heterozygote advantage of the rs3794624 polymorphism in CYBA for resistance to tuberculosis in two chinese populations. Sci Rep. 2016 Nov 30;6:38213
  • Taefehshokr N, Taefehshokr S, Hemmat N, Heit B. Covid-19: Perspectives on innate immune evasion. Front Immunol. 2020 Sep 30;11:580641.
  • Mohan AA, Olson LB, Naqvi IA, Morrison SA, Kraft BD, Chen L, et al. Age and comorbidities predict COVID-19 outcome, regardless of innate immune response severity: A single institutional cohort atudy. Crit Care Explor. 2022 Dec 5;4(12):e0799.
  • Toori KU, Qureshi MA, Chaudhry A, Safdar MF. Neutrophil to lymphocyte ratio (NLR) in COVID-19: A cheap prognostic marker in a resource constraint setting. Pak J Med Sci. 2021 Sep-Oct;37(5):1435-9.
  • Russell CD, Lone NI, Baillie JK. Comorbidities, multimorbidity and COVID-19. Nat Med. 2023 Feb;29(2):334-43.
There are 24 citations in total.

Details

Primary Language English
Subjects Respiratory Diseases, Infectious Diseases, Medical Virology
Journal Section Research Article
Authors

Reviono Reviono This is me 0000-0001-5606-7587

Olivia Geraldine Roxanne 0009-0008-6846-3251

Hendrastutik Apriningsih 0000-0003-3811-2633

Publication Date September 30, 2024
Submission Date November 6, 2023
Acceptance Date July 30, 2024
Published in Issue Year 2024 Volume: 41 Issue: 3

Cite

APA Reviono, R., Roxanne, O. G., & Apriningsih, H. (2024). Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population. Journal of Experimental and Clinical Medicine, 41(3), 479-484.
AMA Reviono R, Roxanne OG, Apriningsih H. Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population. J. Exp. Clin. Med. September 2024;41(3):479-484.
Chicago Reviono, Reviono, Olivia Geraldine Roxanne, and Hendrastutik Apriningsih. “Investigation of HLA DRB1*09:01 Polymorphism and Its Association With COVID-19 Severity in Indonesian Population”. Journal of Experimental and Clinical Medicine 41, no. 3 (September 2024): 479-84.
EndNote Reviono R, Roxanne OG, Apriningsih H (September 1, 2024) Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population. Journal of Experimental and Clinical Medicine 41 3 479–484.
IEEE R. Reviono, O. G. Roxanne, and H. Apriningsih, “Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population”, J. Exp. Clin. Med., vol. 41, no. 3, pp. 479–484, 2024.
ISNAD Reviono, Reviono et al. “Investigation of HLA DRB1*09:01 Polymorphism and Its Association With COVID-19 Severity in Indonesian Population”. Journal of Experimental and Clinical Medicine 41/3 (September 2024), 479-484.
JAMA Reviono R, Roxanne OG, Apriningsih H. Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population. J. Exp. Clin. Med. 2024;41:479–484.
MLA Reviono, Reviono et al. “Investigation of HLA DRB1*09:01 Polymorphism and Its Association With COVID-19 Severity in Indonesian Population”. Journal of Experimental and Clinical Medicine, vol. 41, no. 3, 2024, pp. 479-84.
Vancouver Reviono R, Roxanne OG, Apriningsih H. Investigation of HLA DRB1*09:01 polymorphism and its association with COVID-19 severity in Indonesian population. J. Exp. Clin. Med. 2024;41(3):479-84.