Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS‐CoV‐2 from 946 whole‐exome sequencing data in the Turkish population

Duman, Nilgun; Tuncel, Gülten; Bişgin, Atıl; Bozdoğan, Sevcan Tuğ; Sağ, Şebnem Özemri; Gül, Şeref; Kiraz, Aslıhan; Balta, Burhan; Erdoğan, Murat; Uyanık, Bülent; Canbek, Sezin; Ata, Pınar; Geçkinli, Bilgen Bilge; Ates, Esra Aslan; Alavanda, Ceren; Ozdemir, S Yesim; Sezer, Özlem; Ozgon, G; Gürkan, Hakan; Guler, Kubra; Boğa, İbrahim; Kaya, Niyazi; Alemdar, Adem; Sayan, Murat; Dündar, Munis; Ergören, Mahmut Çerkez; Temel, Şehime Gülsün

doi:10.1002/jmv.27976

Cited by 11 publications

(4 citation statements)

References 41 publications

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“…The clinical presentation of SARS-CoV-2 infection is highly variable, ranging from asymptomatic infection to severe disease with respiratory failure, overactive immune response, and death occurring in about 0.5%–1% of infections ( Salzberger et al, 2021 ). Known risk factors for severe disease course include demographic characteristics (male sex, older age, and ancestry) and chronic diseases such as obesity, as well as cardiovascular, renal, and respiratory disease ( Yang et al, 2020 ; O'Driscoll et al, 2021 ; Sokologorskiy et al, 2022 ), but these factors do not fully explain differences in clinical severity ( Duman et al, 2022 ; Nhung et al, 2022 ; Petersen et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

COVID-19 severity: does the genetic landscape of rare variants matter?

et al. 2023

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Rare variants affecting host defense against pathogens may be involved in COVID-19 severity, but most rare variants are not expected to have a major impact on the course of COVID-19. We hypothesized that the accumulation of weak effects of many rare functional variants throughout the exome may contribute to the overall risk in patients with severe disease. This assumption is consistent with the omnigenic model of the relationship between genetic and phenotypic variation in complex traits, according to which association signals tend to spread across most of the genome through gene regulatory networks from genes outside the major pathways to disease-related genes. We performed whole-exome sequencing and compared the burden of rare variants in 57 patients with severe and 29 patients with mild/moderate COVID-19. At the whole-exome level, we observed an excess of rare, predominantly high-impact (HI) variants in the group with severe COVID-19. Restriction to genes intolerant to HI or damaging missense variants increased enrichment for these classes of variants. Among various sets of genes, an increased signal of rare HI variants was demonstrated predominantly for primary immunodeficiency genes and the entire set of genes associated with immune diseases, as well as for genes associated with respiratory diseases. We advocate taking the ideas of the omnigenic model into account in COVID-19 studies.

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Section: Introductionmentioning

confidence: 99%

COVID-19 severity: does the genetic landscape of rare variants matter?

et al. 2023

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“…The authors from Turkey, Iraq, and Slovenia found no association between the rs2285666 polymorphism and the severity of COVID-19 (Duman et al, 2022;Mahmood et al, 2022;Jevnikar et al, 2022). However, Mahmood et al (2022) reported that the A allele was more commonly detected in the women's case group compared to the control group.…”

Section: Discussionmentioning

confidence: 98%

Distribution of Alleles and Genotypes of ACE2 Gene Polymorphisms (rs2285666 and rs35803318) and Association with COVID-19 Among Populations in Kazakhstan

Bisseneva,

Li,

Pogossyan

et al. 2024

OnLine Journal of Biological Sciences

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There is still no definitive confirmation regarding the association between ACE2 gene polymorphisms and COVID-19. This study was conducted to analyze the distribution of alleles and genotypes of the ACE2 gene rs2285666 and rs35803318 two polymorphisms and their possible association with COVID-19 among two ethnic groups, namely, the Kazakhs and Eastern Slavs, residing within the same geographic area in the city of Karaganda, Republic of Kazakhstan. This research was conducted for the first time in Kazakhstan. The genotyping was performed using the Amplification-Refractory Mutation System (ARMS) PCR. A substantial connection of rs2285666 with COVID-19 in the studied Kazakh and Eastern Slavs populations (p>0.05) was not observed. It has been determined that certain alleles and genotypes serve as protective markers against COVID-19. It was determined that the G allele (p = 0.0217) of rs2285666 among Kazakh men reduced the likelihood of coronavirus infection. It was concluded that the C allele and CC genotype of rs35803318 have a statistically significant association with protection against COVID-19 among only Eastern Slavs. There were no differences in the alleles and genotypes of polymorphism between males and females. Thus, the analysis of the rs2285666 and rs35803318 polymorphisms has revealed that these two variants of the ACE2 gene do not exert an influence on the risk of contracting COVID-19.

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“…In another study from Turkey, the changes in the ACE2 gene were evaluated retrospectively, and 2 nonsynonymous variants were observed. However, the relationship between these variants and COVID-19 disease could not be established (Duman et al 2022). These two nonsynonymous variants (p.Lys26Arg and p.Asn720Asp) in the ACE2 gene were not detected in our study.…”

Section: Sars-covmentioning

confidence: 99%

Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort

Ceylan,

Çavdarlı,

Ceylan

et al. 2023

Tohoku J. Exp. Med.

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The pandemic COVID-19 has caused a high mortality rate and poses a significant threat to the population. The disease may progress with mild symptoms or may cause the need for intensive care, depending on many factors. In this study, it was aimed to determine if there is a tendency due to genetic factors in COVID-19 patients. Ninety-four of 188 patients with mild clinical and 94 with severe clinical symptoms were included in the study. The targeted panel including coagulopathy(F2, F5), viral invasion(ACE2), and inflammation(CXCL8, IFNAR2, IFNL4, IL10, IL2, IL6, IRF7, TLR3, TLR7, TNF) related genes was performed sequenced by NGS. The variants found were classified and univariate analyses were performed to select candidate variables for logistic model. Risk factors and variants were compared. It was revealed that the presence of 2 or more risk factors caused the disease to progress severely(p<0.001). Heterozygous IRF7:c.1357-23dup variant had a 2.5 times higher risk for mild disease compared to severe disease. Other variants were found to be more significant in mild disease. Since polymorphic variants were not evaluated in the literature, the findings of our study could not be compared with the literature. However, as variants that may be effective in the severity of infections may differ according to ethnicity. This study has the feature of being a guide for subsequent studies to be carried out especially in Turkish population. Clinical course of the COVID-19 is likely to depend on a variety of risk factors, including age, sex, clinical status, immunology and genetic factors.

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Analysis of ACE2 and TMPRSS2 coding variants as a risk factor for SARS‐CoV‐2 from 946 whole‐exome sequencing data in the Turkish population

Cited by 11 publications

References 41 publications

COVID-19 severity: does the genetic landscape of rare variants matter?

COVID-19 severity: does the genetic landscape of rare variants matter?

Distribution of Alleles and Genotypes of ACE2 Gene Polymorphisms (rs2285666 and rs35803318) and Association with COVID-19 Among Populations in Kazakhstan

Impact of Inflammation-Related Genes on COVID-19: Prospective Study at Turkish Cohort

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