Association of genetic polymorphisms with COVID-19 infection and outcomes: An updated meta-analysis based on 62 studies
Hongyue Ren, Yanyan Lin, Lifeng Huang, Wenxin Xu, Deqing Luo, Chunbin Zhang
Heliyon, doi:10.1016/j.heliyon.2023.e23662
Background: The relationship between genetic polymorphisms and coronavirus disease 2019 remains to be inconsistent. This meta-analysis aimed to provide an updated evaluation of the role of genetic polymorphisms in the infection, severity and mortality of COVID-19 based on all available published studies. Methods: A systematic search was performed using six databases: PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were used to calculate the genotypic comparison. All statistical analyses were conducted in Stata 12.0. Results: A total of 62 studies with 19600 cases and 28899 controls was included in this metaanalysis. For COVID-19 infection, ACE Ins/Del polymorphism might be related with significantly decreased risk of COVID-19 infection under dominant, homozygote and allelic models. Meanwhile, the IFITM3 rs12252 and TMPRSS2 rs12329760 polymorphisms were significantly associated with the increased risk of COVID-19 infection under one or more models. Regarding COVID-19 severity, ACE2 rs2074192, ACE2 rs2106809, IFITM3 rs12252 and VDR rs1544410 polymorphisms might be related with significantly increased risk of COVID-19 severity in one or more models. Moreover, the analysis of TMPRSS2 rs2070788 indicated that a variant A allele decreased the risk of COVID-19 severity in recessive model. For COVID-19 mortality, the variant C allele of IFITM3 rs12252 polymorphism might be related with significantly increased risk of COVID-19 mortality under all genetic models. Conclusions: This meta-analysis indicated that he infection, severity or mortality of COVID-19 were related to the above genetic polymorphisms, which might provide an important theoretical basis for understanding the clinical feature of COVID-19 disease.
Declaration of competing interest The author (s) declare that they have no competing interests.
Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.heliyon.2023.e23662.
References
Abbaszadeh, Angiotensin-converting enzyme 1 and voltage-gated potassium channel-interacting protein 4 gene polymorphisms in COVID-19 patients from east of Iran, Clin. Chim. Acta
Abdelsattar, ACE2 and TMPRSS2 SNPs as determinants of susceptibility to, and severity of, a COVID-19 infection, Br. J. Biomed. Sci
Abdollahzadeh, Association of Vitamin D receptor gene polymorphisms and clinical/severe outcomes of COVID-19 patients, Infect. Genet. Evol
Abobaker, The impact of certain genetic variants (single nucleotide polymorphisms) on incidence and severity of COVID-19, J. Gene Med
Agwa, Association between interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 variant polymorphisms with the course and outcome of SARS-CoV-2 patients, Genes
Ahmadi, Impact of interferon-induced transmembrane protein 3 gene rs12252 polymorphism on COVID-19 mortality, Cytokine
Akbari, Assessment of ACE1 variants and ACE1/ACE2 expression in COVID-19 patients, Vascul Pharmacol
Al-Anouti, Associations between genetic variants in the vitamin D petabolism rathway and severity of COVID-19 among UAE lesidents, Nutrients
Aladag, Human cce D/I polymorphism could affect the Clinicobiological course of COVID-19, J Renin Angiotensin Aldosterone Syst
Aladawy, Polymorphism in promotor region of IL6 gene as a predictor for severity in COVID -19 patients, Egypt, J. Immunol
Alghamdi, Interferon-induced transmembrane protein-3 genetic variant rs12252 is associated with COVID-19 mortality, Genomics
Ali, Association of tumor necrosis factor alpha -308 single nucleotide polymorphism with SARS CoV-2 infection in an Iraqi Kurdish population, J. Clin. Lab. Anal
Alimoradi, SNPs of ACE1 (rs4343) and ACE2 (rs2285666) genes are linked to SARS-CoV-2 infection but not with the severity of disease, Virol. J
Amodio, SARS-CoV-2 viral ooad, IFN lambda polymorphisms and the course of COVID-19: an ibservational study, J. Clin. Med
Amoroso, HLA and AB0 polymorphisms may influence SARS-CoV-2 infection and COVID-19 severity, Transplantation
Angulo-Aguado, Association between the LZTFL1 rs11385942 polymorphism and COVID-19 severity in Colombian population, Front. Med
Annunziata, The angiotensin converting enzyme deletion/deletion genotype is a risk factor for severe COVID-19: umplication and atility for patients edmitted to dmergency Department, Medicina-Lithuania
Apaydin, Effects of vitamin D receptor gene polymorphisms on the prognosis of COVID-19, Clin. Endocrinol
Balzanelli, Analysis of gene single nucleotide polymorphisms in COVID-19 disease sighlighting the susceptibility and the severity towards the infection, Diagnostics
Bas, Are angiotensin converting enzyme (ACE1/ACE2) gene variants associated with the clinical severity of COVID-19 pneumonia? A single-center cohort study, Anatol, J. Cardiol
Beheshti Shirazi, rs12329760 polymorphism in transmembrane serine protease 2 gene and risk of coronavirus disease 2019 mortality, BioMed Res. Int
Cafiero, Angiotensin system polymorphisms' in SARS-CoV-2 positive patients: assessment between iymptomatic and asymptomatic patients: a pilot study, Pharmacogenomics Personalized Med
Chilamakuri, Agarwal, COVID-19: characteristics and therapeutics, Cells
De Andrade, A polymorphism in the TMPRSS2 gene dncreases the risk of heath in older patients rospitalized with COVID-19, Viruses
Diamond, Farzan, The broad-spectrum antiviral functions of IFIT and IFITM proteins, Nat. Rev. Immunol
Dieter, Genetic polymorphisms associated with susceptibility to COVID-19 disease and severity: a systematic review and meta-analysis, PLoS One
Djaharuddin, Comorbidities and mortality in COVID-19 patients, Gac. Sanit
Dobrijevic, The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with COVID-19 severity: a systematic review and metaanalysis, Excli j
Falahi, Evaluation of the relationship between IL-6 gene single nucleotide polymorphisms and the severity of COVID-19 in an Iranian population, Cytokine
Faridzadeh, The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: a case-control study, Front. Genet
Gong, Angiotensin-converting enzyme genotype-specific immune cesponse nontributes to the susceptibility of COVID-19: a rested case-control study, Front. Pharmacol
Gunal, Angiotensin-converting enzyme-1 gene insertion/deletion polymorphism may be associated with COVID-19 clinical severity: a prospective cohort study, Ann. Saudi Med
Gómez, Angiotensin-converting enzymes (ACE, ACE2) gene variants and COVID-19 outcome, Gene
Gómez, The Interferon-induced transmembrane protein 3 gene (IFITM3) rs12252 C variant is associated with COVID-19, Cytokine
Hubacek, ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors, Clin. Chim. Acta
Jafarpoor, VDR gene polymorphisms are associated with the increased susceptibility to COVID-19 among iranian population: a case-control study, Int. J. Immunogenet
Jevnikar, The role of ACE, ACE2, and AGTR2 polymorphisms in COVID-19 severity and the presence of COVID-19-related detinopathy, Genes
Jin, Gender differences in patients with COVID-19: rocus on severity and mortality, Front. Public Health
Karakas, Çelik, Polymorphisms of ACE (I/D) and ACE2 receptor gene (Rs2106809, Rs2285666) are not related to the clinical course of COVID-19: a case study, J. Med. Virol
Kerget, Kerget, Frequency of interleukin-6 rs1800795 (-174G/C) and rs1800797 (-597G/A) polymorphisms in COVID-19 patients in Turkey who mevelop aacrophage zctivation syndrome, Jpn. J. Infect. Dis
Khalilzadeh, Angiotensin-converting enzyme 2 rs2285666 polymorphism and clinical parameters as the determinants of COVID-19 severity in Iranian population, Int. J. Immunogenet
Knobloch, Preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement and publication bias, J. Cranio-Maxillo-Fac. Surg
Kotur, Association of vitamin D, sinc and helenium related genetic variants with COVID-19 disease severity, Front. Nutr
Lapić, Association of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with disease severity in COVID-19 patients: a pilot study, J. Med. Virol
Mahdi, Assessing the potential correlation of polymorphisms in the TMPRSS2 gene with severity of COVID 19 patients, Biomedicine
Martínez-Gómez, ACE and ACE2 gene variants are associated with severe outcomes of COVID-19 in men, Front. Immunol
Meltzer, Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence
Mir, Strong association of angiotensin converting enzyme-2 gene insertion/deletion polymorphism with susceptibility to SARS-CoV-2, aypertension, coronary Artery disease and COVID-19 disease mortality, Pharmacogenetics Genom
Mohlendick, ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19, Mol. Genet. Genom
Molina, Polymorphisms in ACE, ACE2, AGTR1 genes and severity of COVID-19 disease, PLoS One
Mortazavi-Tabatabaei, Pattern of rntibacterial uesistance in trinary Tract infections: a systematic review and meta-analysis, Int. J. Prev. Med
Najafi, Mahdavi, Association investigations between ACE1 and ACE2 polymorphisms and severity of COVID-19 disease, Mol Genet Genomics
Nhung, Host genetic risk factors associated with COVID-19 susceptibility and severity in Vietnamese, Genes
Organization, Clinical Management of COVID-19, Living Guideline
Pan, Association between rs12252 polymorphism in IFITM3 gene and COVID-19, Int. J. Virol
Papadopoulou, Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: a rather controversial hypothesis. A case-control study, J. Med. Virol
Peralta, TaqI polymorphism of the VDR gene: aspects related to the clinical behavior of COVID-19 in Cuban patients, Egyptian Journal of Medical Human Genetics
Posadas-Sanchez, Association of the transmembrane serine protease-2 (TMPRSS2) polymorphisms with COVID-19, Vasc. Pharmacol
Rahimi, The association between interferon lambda 3 and 4 gene single-nucleotide polymorphisms and the recovery of COVID-19 patients, Virol. J
Ren, None
Ren, None
Reviono, Frequency of Interleukin-6 rs 1800796 (-572G/C) TNF-? rs1800750 (-376G/A), and 1800629 (-308G/A) polymorphism in COVID-19 patients with clinical degrees in Central Java, Bali Med. J
Rokni, Association of TMPRSS2 gene polymorphisms with COVID-19 severity and mortality: a case-control study with pomputational analyses, Appl. Biochem. Biotechnol
Saad, The role of angiotensin converting enzyme 1 insertion/deletion genetic polymorphism in the risk and severity of COVID-19 infection, Front. Med
Saengsiwaritt, Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID-19 severity: a systematic review with meta-analysis, Rev. Med. Virol
Saleh, Association of TNF-alpha G-308 a oromoter polymorphism with the course and outcome of COVID-19 patients, Immunol. Invest
Schoenfelder, Transmembrane serine protease 2 polymorphisms and susceptibility to severe acute respiratory syndrome coronavirus type 2 infection: a German case-control study, Front. Genet
Schönfelder, The influence of IFITM3 polymorphisms on susceptibility to SARS-CoV-2 infection and severity of COVID-19, Cytokine
Sekiya, TMPRSS2 gene polymorphism common in East Asians confers decreased COVID-19 susceptibility, Front. Microbiol
Shang, Cell entry mechanisms of SARS-CoV-2, Proc Natl Acad Sci U S A
Shi, An overview of COVID-19, J. Zhejiang Univ. -Sci. B
Sienko, Association of ACE2 gene variants with the severity of COVID-19 disease-A prospective Observational study, Int J Environ Res Public Health
Sotomayor-Lugo, The role of tumor necrosis factor alpha-308A > G polymorphism on the clinical states of SARS-CoV-2 infection, Hum. Genom
Stang, Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses, Eur. J. Epidemiol
Tipnis, A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase, J. Biol. Chem
Verma, Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity, Int. J. Immunogenet
Verma, Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients, Infect. Genet. Evol
Vitello, Allelic variations in the human genes TMPRSS2 and CCR5, and the Resistance to viral infection by SARS-CoV-2, Int. J. Mol. Sci
Wu, Mcgoogan, Characteristics of and important oessons from the coronavirus disease 2019 (COVID-19) sutbreak in China: pummary of a report of 72 314 cases from the Chinese center for disease control and frevention, JAMA
Wulandari, Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients, Hum Genomics
Zeidan, Vitamin D deficiency and vitamin D receptor FokI polymorphism as risk factors for COVID-19, Pediatr. Res
Zhang, Interferon-induced transmembrane protein 3 genetic variant rs12252-C associated with disease severity in coronavirus disease 2019, J. Infect. Dis
