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1.
Sci Rep ; 14(1): 15058, 2024 07 01.
Article in English | MEDLINE | ID: mdl-38956433

ABSTRACT

Since the COVID-19 pandemic, the diversity of clinical manifestations in patients has been a tremendous challenge. It seems that genetic variations, as one of the players, contribute to the variety of symptoms. Genome-wide association studies have demonstrated the influence of certain genomic regions on the disease prognosis. Particularly, a haplotype at 3p21.31 locus, inherited from Neanderthals, showed an association with COVID-19 severity. Despite several studies regarding this haplotype, some key variants are not sufficiently addressed. In the present study, we investigated the association of rs17713054 at 3p21.31 with COVID-19 severity. We analyzed the genotype of 251 Iranian COVID-19 patients (151 patients with asymptomatic to mild form as control and 100 patients with severe to critical symptoms without any comorbidities as case group) using the ARMS-PCR method. Results demonstrated that the A allele confers an almost twofold increased risk for COVID-19 severity (P value = 0.008). The AA genotype also raises the risk by more than 11 times following the recessive model (P value = 0.013). In conclusion, the A allele in rs17713054 was a risk allele in Iranian patients and was independently associated with COVID-19 severity. More studies are beneficial to confirm these findings in other populations and to develop strategies for risk assessment, prevention, and personalized medicine.


Subject(s)
COVID-19 , Genetic Predisposition to Disease , Neanderthals , Polymorphism, Single Nucleotide , SARS-CoV-2 , Severity of Illness Index , Humans , COVID-19/genetics , COVID-19/virology , COVID-19/epidemiology , Iran/epidemiology , Neanderthals/genetics , Male , Female , Middle Aged , Animals , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Adult , Haplotypes , Chromosomes, Human, Pair 3/genetics , Alleles , Genome-Wide Association Study , Genotype , Aged
2.
PLoS One ; 18(2): e0281750, 2023.
Article in English | MEDLINE | ID: mdl-36795725

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients' peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/genetics , SARS-CoV-2 , Iran/epidemiology , Polymorphism, Genetic , Genetic Predisposition to Disease , Serine Endopeptidases/genetics
3.
Pak J Pharm Sci ; 33(5): 1939-1943, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33824099

ABSTRACT

In the Streptococcus pneumoniae, the N-acetylmuramoyl-l-alanine amidase known as LytA protein is a main autolysin and in the presence of sodium deoxycholate, it activates and breaks S. pneumoniae cell wall. In the present study, the interaction between the LytA protein and deoxycholate as ligand was investigated. The Lyt A protein was retrieved from PDB databank and energetically minimized by Molegro Virtual Docker. The binding sites of LytA protein were detected and molecular docking carried out using MolDock algorithm. Finally, the number of hydrogen and electrostatic bonds were obtained for each predicted pose. A total of 5 binding sites predicted on LytA protein. The number of 5 predicted poses for each binding site also detected and molecular docking showed that all the poses have interactions (by H bonds) with deoxycholate. The interaction of the LytA protein with the deoxycholate ligand reveal five binding sites, which are involved in deoxycholate substrate recognition.


Subject(s)
Bacterial Proteins/metabolism , Deoxycholic Acid/metabolism , Molecular Docking Simulation , N-Acetylmuramoyl-L-alanine Amidase/metabolism , Streptococcus pneumoniae/enzymology , Bacterial Proteins/chemistry , Binding Sites , Deoxycholic Acid/chemistry , Enzyme Activation , Hydrogen Bonding , Ligands , N-Acetylmuramoyl-L-alanine Amidase/chemistry , Protein Binding , Protein Conformation , Structure-Activity Relationship
4.
J Adv Pharm Technol Res ; 9(3): 73-79, 2018.
Article in English | MEDLINE | ID: mdl-30338232

ABSTRACT

Rhinoplasty is done with external and endonasal methods. One of the main stages of rhinoplasty in both external and endonasal methods is the lateral nasal osteotomy. Lateral nasal osteotomy is the main cause of edema and ecchymosis after rhinoplasty, which is annoying and unpleasant for patients. Piezosurgery is a new method that uses electronic-ultrasonic waves to perform nasal osteotomies. The aim of this study was to compare of edema and ecchymosis after lateral nasal osteotomy using piezosurgery with external osteotomy in rhinoplasty candidates. In this clinical trial, 66 experimental patients for rhinoplasty surgery were selected from Imam Reza hospital in Tabriz, Iran. After examination, the patients were randomly divided into two groups. One group of patients had lateral nasal osteotomy by using the piezosurgery technique, and the other group had a lateral osteotomy with the conventional method of external subcutaneous. On the third and 7 days after the operation, the level of edema and ecchymosis in the patients were examined as per the Gökalan questionnaire (adopted by Yucel) by two persons who were not aware of the goals of the study, and then, they evaluated and scored the questionnaire. The obtained data were analyzed by the SPSS 19 software. The highest level of edema and ecchymosis was observed 3 days after surgery in both groups. Meanwhile, the findings revealed a significant difference between the two groups in the amount of edema and ecchymosis on day 3 after surgery. Furthermore on day 7, the amount of edema and ecchymosis compared to that of the 3rd day was statistically significant for both groups. In general, in all studied groups, edema, and ecchymosis decreased in 7 days compared to 3 days and also piezosurgery is more promising and effective than osteotomy.

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