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      Is There a Link between COVID-19 Mortality with Genus, Age, ABO Blood Group Type, and ACE2 Gene Polymorphism?

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          Abstract

          Dear Editor-in-Chief A group of pneumonia patients in Wuhan created an alarm worldwide by the end of December 2019. This emerging pneumonia soon became as a novel coronavirus (2019-nCoV or COVID-19) (1). More than 80% of individuals with COVID-19 have a “mild illness and will heal” whereas it is lethal in 2% of reported cases (2). The age and sex of individuals are two risk factors of COVID-19 susceptibility and its clinical outcome (3). It is therefore highly important to specify briskly the odds ratio for mortality adjusted to comorbidities that are highly prevalent globally, by age and sex, to prevent COVID-19 specific mortality (4). We aimed to compute the relationship between the ABO blood type, age, sex, and ACE2 gene polymorphism with the susceptibility to COVID-19 in patients from Iran to test if the former can act as a biomarker for the latter. Our study was performed on 94 random samples of dead cases infected with SARS-CoV-2. Of these, only 76 were identified by blood type. A recent survey of ABO blood group distribution of 80,982,137 normal people from Iran was used as comparison controls for patients with COVID-19 (https://en.wikipedia.org/wiki/Blood_type_distribution_by_country). Then, statistical analysis was performed using SPSS software version 15 (Chicago, IL, USA). The ABO blood group in 80,982,137 normal people and 76 dead patients with COVID-19 is showed in Table 1. People with type A phenotype were substantially more likely to become infected with 2019-nCoV (95% CI, P= 0.014, Fig. 1A). The O, AB and B blood groups seemed to have a lower risk of infection, although the associations did not reach statistical significance (Table 1). Fig. 1: The chart of ABO blood group, genus, and age distribution in patients with COVID-19 Table 1: The relationship of COVID-19 with ABO blood group, age, and genus Variable Blood Group A B AB O Controls (Iran) 80,982,137 30% 24.7% 7.8% 37.5% Death cases 76 34 (44.7%) 17 (22.4%) 4 (5.3%) 21 (27.6%) χ2 6.000 0.383 1.385 3.030 P 0.014 0.536 0.239 0.082 Genus Male 73 (77.7%) Female 21 (22.3%) χ2 28.766 P < 0.001 Age (yr) <20 1(1.1%) 20–39 7(7.4%) 40–59 36 (38.3%) 59< 50 (53.2%) Mann-Whitney Test 40 − 59 59 < P value = 0.004 We noticed that ABO blood groups exhibited various association risks for the infection with SARS-CoV-2 resulting in COVID-19. Our results similar to another one (3), in Wuhan, China showed blood group A was significantly associated with a higher risk of infection and blood group O was associated with a lower risk (3). Moreover, we analyzed the people’s age and sex as two other risk factors among patients with COVID-19 where the COVID-19 mortality rate for men was four times more than that of women. The genus of dead patients was 73 men and 21 women. These results corresponded to a significantly increased risk of men in comparison with women for COVID-19 (Fig. 1B) (P< 0.001). Also, current survey suggested that patients with ages of 50 < years are at greater risk relative to children who might be less likely to become infected or may show milder signs or even asymptomatic infection (P= 0.004). A dead case with the “age of 94 is also shown in Table 1 and Fig. 1C. “Angiotensin-converting enzyme 2 (ACE2) is an enzyme attached to the outer surface (cell membranes) of cells in the lungs, arteries, heart, kidney, and intestines “(https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_2). ACE2 is known as SARS-CoV-2 receptor and balance of ACE-ACE2 axis and blood pressure are important in patients with COVID-19 and susceptibility to the disease. Association between genotype of ACE2-ACE axis, blood group A, and blood pressure has been previously reported (5, 6). Despite the genetic differences between Chinese and Iranian nations in ACE-ACE2 axis (7), people with blood group A in both nations are more susceptible to COVID-19 and risk of death.

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          Coronavirus: covid-19 has killed more people than SARS and MERS combined, despite lower case fatality rate

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            The geographic distribution of the ACE II genotype: a novel finding

            Angiotensin converting enzyme (ACE) gene polymorphism insertion (I) or deletion (D) has been widely studied in different populations, and linked to various functional effects and associated with common diseases. The purpose of the present study was to investigate the relationship between the ACE I/D frequency in different populations and geographic location; ACE I/D allele frequency in the Lebanese population and ACE II genotype contribution to the geographic trend were also identified. Five hundred and seventy healthy volunteers were recruited from the Lebanese population. Genomic DNA was extracted from buccal cells, and amplified by polymerase chain reaction; products were then identified by gel electrophoresis. The frequencies of the different ACE I/D genotypes were determined and tested for Hardy–Weinberg equilibrium (HWE). To assess the relationship between ACE I/D frequency and geographic location, and to identify how the Lebanese population contributes to the geographic trend in ACE I/D frequencies, Eurasian population samples and Asians were incorporated in the analyses from the literature. The frequency of the I allele in the Lebanese population was 27% and the corresponding II genotype was at a frequency of 7·37% (in HWE; P =0·979). The ACE I allele and genotype frequencies show an association with longitude, with frequencies increasing eastwards and westwards from the Middle East.
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              Association analysis of 24-h blood pressure records with I/D ACE gene polymorphism and ABO blood group system.

              The purpose of this study was to analyze the association between 24-h blood pressure parameters, insertion/deletion polymorphism of the angiotensin I converting enzyme gene and the ABO blood group system in a sample of the general Czech population. Fourteen parameters describing the 24-h blood pressure readings were obtained by analyzing blood pressure records in 243 volunteers, 119 men and 124 women. These parameters were adjusted for sex and body mass index (BMI) by means of multiple regression test. All subjects were genotyped for the insertion/deletion polymorphism of angiotensin I converting enzyme (I/D ACE) gene and routinely examined for the blood group phenotype in the ABO system. An association was found between the interaction of I/D ACE gene polymorphism and ABO blood group system on the one hand and mean values of systolic (p=0.016) or mean arterial (p=0.027) blood pressures and the phase shift of 24-h BP rhythm (p=0.036) on the other hand. Among three I/D ACE variants the DD genotype was associated with the highest values of mean blood pressure in blood group A and AB carriers. The same genotype was associated with the lowest blood pressures in blood group B and O carriers. In subjects with the DD genotype, the earlier daily position of the maximum of 24-h BP rhythm was found in blood group B, AB and O carriers. On the contrary, blood group A was associated with the latest position of maximum of the 24-h BP rhythm in the DD genotypes.
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                Author and article information

                Journal
                Iran J Public Health
                Iran J Public Health
                IJPH
                IJPH
                Iranian Journal of Public Health
                Tehran University of Medical Sciences
                2251-6085
                2251-6093
                August 2020
                : 49
                : 8
                : 1582-1584
                Affiliations
                [1. ]Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
                [2. ]Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
                [3. ]Department of Biology, Imam Hossein University, Tehran, Iran
                [4. ]Department of Parasitology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
                [5. ]Institute of Policy Research and Social Studies, Tehran, Iran
                Author notes
                [* ] Corresponding Author: Email: hasan_zm@ 123456modares.ac.ir
                Article
                IJPH-49-1582
                10.18502/ijph.v49i8.3910
                7554399
                445bbb5d-886a-4a54-b4ac-872ac6290158
                Copyright© Iranian Public Health Association & Tehran University of Medical Sciences

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 June 2020
                : 18 June 2020
                Categories
                Letter to the Editor

                Public health
                Public health

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