Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis

Keikha, Masoud

doi:10.1016/j.micpath.2022.105781

Cited by 10 publications

(12 citation statements)

References 64 publications

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“…The results of the study in Baghdad and Anbar governorates agreed with [12], who found that the elevation of the DD mutant genotype at rs4646994 based on geographic region and ethnicity is a predictive biomarker for determining human susceptibility to SARS-CoV-2 infection and the severity of its symptoms, as it is This pattern could significantly increase the risk of SARS-CoV-2 infection by 1.7-fold in the Asian population, in contrast to the results for Erbil Governorate in which the heterozygous ID genotype had the highest frequency. While he indicated that the normal genotype II was more resistant to the severity of COVID-19, and the results of the frequency ratio of the mutant allele D to the normal allele I agreed with Anbar and Erbil governorates that it constitutes a risk factor for the disease with what the same researcher found for patients infected with SARS-CoV -2.…”

Section: The Percentage Genotypes and Allele Frequency Of The Ace-1 G...supporting

confidence: 76%

“…The results showed in Table (9) the percentage of genotypes of the ACE-1 gene at the rs4646994 site for three genotypes (II, ID, DD) for the two groups of COVID-19 patients and healthy people in Anbar Province, the highest frequency of individuals carrying the mutant genotype DD was ( 66.66 %) for the patient's group compared to (27.27 %) for the healthy group. For individuals carrying the homozygous genotype II, the frequency rate was (20%) and (27.27 %) for patients and healthy people, respectively, and the lowest frequency rate for individuals carrying the heterozygous genotype ID was (13.34%) ) and (45.45%) for the sick and healthy group, respectively.…”

Section: The Percentage Genotypes and Allele Frequency Of The Ace-1 G...mentioning

confidence: 99%

“…A correlation was found between the ACE2 SNP rs233575 and blood pressure, and ACE2 risk alleles were associated with more severe COVID-19 outcomes in obese, smoking males [8]. Depending on the geographic region, the rs4646994 DD genotype can be considered as a predictive biomarker for determining human susceptibility to SARS-CoV-2 infection and severe outcome to COVID-19, as studies have indicated that individuals with GG and TT genotypes are significantly more susceptible to severe outcome disease, whereas, conversely, individuals with GA, AA, and CC genotypes are less likely to develop severe COVID-19 [9] Wang and Corpe, studying ACE2 SNPs that included ACE2 SNPs rs2074192, rs6632677, rs4646142, rs2048683, and rs4240157 for the first time in COVID-19 patients using genotyping assays, found that there is a relationship between genetic polymorphisms and allele frequency of ACE2 SNPs and disease severity. [10].…”

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confidence: 99%

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Relationship of ACE1 and ACE2 genetic polymorphisms on SARS-CoV-2 infection and severity of symptoms in different regions of Iraq

Khashan,

Thalij,

Yaseen

2024

Tikrit J. Pure Sci.

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This study was conducted in the laboratories of the Biology Department - College of Science - Tikrit University, the laboratories of the Food Science Department - College of Agriculture - University of Anbar, and the Public Health Laboratories - Anbar for the period from December 2021 AD until February 2022 AD, study involved taking samples from hospitalized COVID-19 patients of both sexes, after a confirmed positive PCR test result. As well as those lying in quarantine in three Iraqi governorates (the isolation unit in Karkh, Yarmouk and Kadhimiya hospitals, the Al-Shifa quarry hospital in Anbar, the public health laboratory in Anbar, and the quarantine hospital for thousands in Erbil), in addition to outpatient clinics. They were distributed by 30 patients and 20 healthy subjects from each governorate, with ages ranging from 18-80 years, randomly to men and women in order to determine the role of genetic polymorphisms in the ACE inhibitor gene in the study samples. The results of the genetic polymorphisms of ACE-1rs4646994, ACE-2rs2106809, and ACE-2rs4240157 showed that there were non-significant differences between the frequency of alleles and genotypes in the patient's group compared with the healthy group. The DD mutant genotype of ACE-1rs4646994 appeared in the patient's group in Baghdad and Anbar with a high percentage, while patients in Erbil showed the highest percentage of the heterozygous genotype ID compared to healthy subjects, with an OR= 0.922, OR= 2.750, and OR= 1.118, respectively, for the mutant allele D. Therefore, it is not considered a risk factor for the disease in Baghdad, in contrast to Anbar and Erbil. The polymorphism of ACE-2rs2106809, the homozygous genotype CC was dominant in patients in the aforementioned provinces and may not be considered a risk factor for the disease. The results of ACE-2rs4240157 gene polymorphism, the heterozygous CT genotype showed a high percentage in patients in Baghdad and, while in Anbar patients, the normal genotype TT appeared to be the highest percentage compared to healthy subjects. The C mutant allele in Baghdad, Anbar, and Erbil patients reached OR= 1.306, OR= 4.333, and OR= 9.00, respectively, so this allele is considered a risk factor for the disease. We can conclude from this study the role of each of the polymorphisms rs4646994 ACE-1 and rs4240157 ACE-2 in infection with COVID-19 and the severity of its symptoms according to the geographical region and race, in contrast to rs2106809 ACE-2, as it is possible to conduct clinical studies to demonstrate the role of genetic polymorphisms with Relationship to diseases depending on the region and race.

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Section: The Percentage Genotypes and Allele Frequency Of The Ace-1 G...supporting

confidence: 76%

Section: The Percentage Genotypes and Allele Frequency Of The Ace-1 G...mentioning

confidence: 99%

mentioning

confidence: 99%

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Relationship of ACE1 and ACE2 genetic polymorphisms on SARS-CoV-2 infection and severity of symptoms in different regions of Iraq

Khashan,

Thalij,

Yaseen

2024

Tikrit J. Pure Sci.

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“…Several previous single-gene association studies and systematic reviews implicated common polymorphisms within the RAAS loci in COVID-19-associated phenotypes. 46,47 Nevertheless, our FUMA-guided gene overlap analysis did not uncover any loci encoding the proteins of RAAS as shared between hypertension and hospitalized COVID-19.…”

Section: Hypertension-driven Pathways Influencing Covid-19mentioning

confidence: 71%

Causal associations and shared genetics between hypertension and COVID‐19

Baranova

Cao

Zhang

2023

Journal of Medical Virology

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To evaluate the genetic relationship between hypertension and COVID-19 and explore the molecular pathways linking hypertension to COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess potential associations between hypertension and hospitalized COVID-19. We compared genome-wide association signals to reveal shared genetic variation between hypertension and hospitalized COVID-19. Moreover, hypertension-driven molecular pathways were constructed based on large-scale literature data to understand the influence of hypertension on COVID-19 at the molecular level. Hypertension has a positive genetic correlation with COVID-19 (r g = 0.19). The MR analyses indicate that genetic liability to hypertension confers a causal effect on hospitalized COVID-19 (odds ratio [OR]: 1.05, confidence interval [CI]: 1.00-1.09, p = 0.030). Hypertension and hospitalized COVID-19 have three overlapping loci and share eight protein-coding risk genes, including ABO, CSF2, FUT2, IZUMO1, MAMSTR, NPNT, RASIP1, and WNT3. Molecular pathway analysis suggests that hypertension may promote the development of COVID-19 through the induction of inflammatory pathways. Our study suggests that genetically determined hypertension may increase the risk for severe COVID-19. The shared genetic variation and the connecting molecular pathways may underline causal links between hypertension and COVID-19.

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“…Several studies have investigated the association of rs2285666 (ACE2) and rs12329760 (TMPRSS2) with COVID-19 severity [ 35 , 36 , 43 , 44 , 45 ]. Interestingly, these studies have either confirmed [ 13 , 36 , 46 , 47 , 48 , 49 , 50 , 51 ] or contradicted [ 52 , 53 , 54 , 55 ] the association between rs2285666 and/or rs12329760 with COVID-19 severity.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms within the SARS-CoV-2 Human Receptor Genes Associate with Variable Disease Outcomes across Ethnicities

Adimulam,

Arumugam,

Naidoo

et al. 2023

Genes

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The contribution of human genes to the variability of disease outcomes has been shown to be important across infectious diseases. Studies have shown mutations within specific human genes are associated with variable COVID-19 outcomes. We focused on the SARS-CoV-2 receptors/co-receptors to identify the role of specific polymorphisms within ACE2, TMPRSS2, NRP1 and CD147. Polymorphisms within ACE2 (rs2285666), TMPRSS2 (rs12329760), CD147 (rs8259) and NRP1 (rs10080) have been shown to associate with COVID-19 severity. Using cryopreserved samples from COVID-19-positive African, European and South Asian individuals within South Africa, we determined genotype frequencies. The genetic variant rs2285666 was associated with COVID-19 severity with an ethnic bias. African individuals with a CC genotype demonstrate more severe COVID-19 outcomes (OR = 7.5; 95% CI 1.164–80.89; p = 0.024) compared with those with a TT genotype. The expressions of ACE2 and SARS-CoV-2 viral load were measured using droplet digital PCR. Our results demonstrate rs2285666 and rs10080 were significantly associated with increased SARS-CoV-2 viral load and worse outcomes in certain ethnicities. This study demonstrates two important findings. Firstly, SARS-CoV-2 viral load is significantly lower in Africans compared with individuals of European and South Asian descent (p = 0.0002 and p < 0.0001). Secondly, SARS-CoV-2 viral load associates with specific SARS-CoV-2 receptor variants. A limited number of studies have examined the receptor/co-receptor genes within Africa. This study investigated genetic variants within the SARS-CoV-2 receptor/co-receptor genes and their association with COVID-19 severity and SARS-CoV-2 viral load across different ethnicities. We provide a genetic basis for differences in COVID-19 severity across ethnic groups in South Africa, further highlighting the importance of further investigation to determine potential therapeutic targets and to guide vaccination strategies that may prioritize specific genotypes.

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Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis

Cited by 10 publications

References 64 publications

Relationship of ACE1 and ACE2 genetic polymorphisms on SARS-CoV-2 infection and severity of symptoms in different regions of Iraq

Relationship of ACE1 and ACE2 genetic polymorphisms on SARS-CoV-2 infection and severity of symptoms in different regions of Iraq

Causal associations and shared genetics between hypertension and COVID‐19

Polymorphisms within the SARS-CoV-2 Human Receptor Genes Associate with Variable Disease Outcomes across Ethnicities

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