The Impact of Surfactant Protein\u2010D Gene Polymorphism on COVID\u201019 Clinical Outcomes

Background: Asthma, a chronic inflammatory respiratory disorder, is influenced by genetic and environmental factors. Allergic asthma is becoming more common because of higher levels of air pollution. Interleukin-4 (IL-4) plays an important role in allergic inflammation and causes the expression of vascular cell adhesion molecule-1. Objective: The present study aims to shed light on the association between cytokine genetic polymorphisms and asthma in Iraqi patients, and to determine their impact on the risk of disease, under the scope of the following: (1) IL-4 cytokines, in terms of their serum level. (2) Assessment of the polymorphisms in the promoter regions of the IL-4, genes in asthma disease patients was carried out, and then their impact on the profile of investigated cytokines was evaluated. Such a collective evaluation may aid in a better understanding of etiopathogenesis in the asthma disease. Materials and Methods: A case-control study was conducted that included 100 participants divided into a patient group (n = 50) with bronchial asthma and a healthy group as a control (n = 50) without asthma. Blood specimens were collected from participants at Marjan Hospital, Babylon Governorate. Serum levels of IL-4 were estimated by an enzyme-linked immunosorbent assay (ELISA) kit. IL4-590 gene polymorphism was detected using amplification refractory mutation system polymerase chain reaction (PCR) with specific primer sequences. Results: The mean concentrations of serum IL-4 were significantly higher in patients having asthma compared to the healthy group (149.84 vs. 53.50, P < 0.0001). In terms of allele and genotype frequencies, the TT genotype was shown to be less common in asthma group compared to controls (4% vs. 22%), whereas the CT genotype was more common in asthma patients (34% vs. 16%). The CC genotype was similar between the two groups. The T allele was more frequent in healthy (39%) compared to asthmatic group (12%), whereas the C allele frequency was higher in asthma patients (61%) compared to controls (88%). Conclusion: This study suggests that gene polymorphism of IL4-590 is associated with risk of developing asthma. Asthma patients have elevated levels of IL-4 and a lower frequency of the TT genotype, indicating an increased likelihood of developing asthma when carrying the T allele and TT genotype. Conversely, the C allele may have a protective influence against asthma development.

The association between a Fatty Acid Binding Protein 1 (FABP1) gene polymorphism and serum lipid abnormalities in the MASHAD cohort study

Tetra amplification refractory mutation system polymerase chain reaction technique (tetra ARMS PCR)ARMS-PCR method was used to genotyping of IL-17A and IL-17F , The impact of IL-17A and IL-17Fgenotypes on the production of interleukins in IBD patients and control groups were determined andInterleukins gene polymorphisms role in IBD infection. significant deference at (p ? 0.05 ) for each rs763780in IL-17 F in patients especially Genotype TT,TC,CC were 31 (51.67%),19 (31.67%),10 (16.67%) \ andrs2275913 in IL-17 A in patients especially Genotype GG,GA,AA were 18 (30%),23 (38.33%),19 (31.67%).As well as genotyping of rs763780 in IL-17 F showed significant increase at a significant level of P?0.05in both TC and CC genotypes in the cases samples compared with the control samples. the odds ratio was2.8894 and 22.3333 for TC and CC genotypes respectively at confidence interval up to 7.8 and 397 forboth genotypes. T allele are more frequent in both cases and control and it have odds ratio as 5.021 Andgenotyping of rs2275913 in IL-17 A showed significant increase at a significant level of P?0.01 for the AAgenotyping in the cases samples compared with the control samples, while the GA genotyping did not showany significant differences, ), the odds ratio for GA genotypes was 2.3590 at confidence interval up to 5.8,while it was 8.4444 at confidence interval up to 32.9 for AA genotypes. G allele are more frequent in bothcases and control and it have odds ratio as 3.319 at confidence interval up to 6

he prevalence of coronavirus disease 2019 (COVID-19) has posed a great threat to people's health worldwide, bringing a great challenges to the public healthcare systems. A recent study has confirmed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses severe acute respiratory syndrome coronavirus (SARS-CoV) receptor angiotensin-converting enzyme 2 (ACE2) for host cell entry. 1 ACE2 expression was previously found to correlate with susceptibility to SARS-CoV infection in vitro.

Following its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused what rapidly became a global pandemic. The precise origin and subsequent path of transmission have not yet been established-but like the other novel coronaviruses that it closely resembles, it appears to have evolved naturally in a bat host. The disease caused by SARS-CoV-2 infection, designated as coronavirus disease 2019 (COVID-19), ranges from asymptomatic, to mild self-limited illness, to progressive pneumonia, respiratory compromise, multiorgan failure, and death. In addition, a hyperinflammatory disease state occurs in a subset of patients, and may be seen either during acute infection or following recovery. The search for effective pharmacological management of COVID-19 continues, but several promising candidates have been identified, including the viral nucleoside analog remdesivir. However, despite the existence of literally thousands of clinical trials, the management of COVID-19 remains challenging, and the development of an optimal, evidence-based therapeutic approach is ongoing. The impact of SARS-CoV-2 and COVID-19 on the biobanking world is evolving and profound-in particular, it is likely that many of mysteries surrounding COVID-19 will be solved via the availability of high-quality, large-scale collection, storage, and analysis of patient specimens. The purpose of this review article is therefore to provide a rapid, comprehensive, and relevant overview and primer on SARS-CoV-2 and COVID-19, with attention to the epidemiology, virology, transmission, clinical features, and major therapeutic options currently existent.

The present coronavirus disease 2019 (COVID‐19) is spreading rapidly and existing data has suggested a number of susceptibility factors for developing a severe course of the disease. The current case‐control experiment is aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID‐19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra‐amplification refractory mutation system polymerase chain reaction technique was recruited to detect −308G>A TNFα and +252A>G TNFβ polymorphisms among the Iranian subjects. We demonstrated that carriers of the G allele of TNFβ‐252A/G, rs909253 A>G were more frequent in COVID‐19 subjects compared to the healthy group and this allele statistically increased the disease risk (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.23–1.96, p < 0.0001). At the same time, the A allele of TNFα‐311A/G, rs1800629 G>A moderately decreased the risk of COVID‐19 (OR = 0.68, 95% CI = 0.53–0.86, p < 0.002). Also, we analyzed the various genotypes regarding the para‐clinical and disorder severity; we found that in the AA genotype of TNFβ‐252A/G (rs909253 A>G), the computed tomography scan pattern was different in comparison to cases carrying the AG genotype with p 1 < 0.001. In addition, in the severe cases of COVID‐19, leukocyte and neutrophil count and duration of intensive care unit hospitalization in the deceased patients were significantly increased (p < 0.001). Moreover, the TNFα‐311A/G (rs1800629 G>A) variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFβ polymorphisms and severe acute respiratory syndrome coronavirus 2. Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID‐19 in other ethnicities.

Hashimoto's thyroiditis (HT) is a chronic inflammation of the thyroid gland and is known as the most common autoimmune disease. Development of autoimmune destruction of thyroid cells is a multi-step process involving convergence of genetic and environmental factors. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) has an important role in homeostasis and negative regulation of immune responses, and is therefore considered to be a key element in the development of autoimmune diseases. The present study evaluated the association of the CTLA-4 gene polymorphisms 318C/T (rs5742909) and +49A/G (rs231775) with HT in an Iranian population (including 82 patients with HT and 104 healthy controls who were referred for routine premarital blood screenings). Genotyping was performed using the tetra-primer amplification refractory mutation system polymerase chain reaction technique. No significant differences were observed in genotype and allele frequencies in the single nucleotide polymorphisms (SNPs) between cases and controls. In the cases as well as in the controls, the TT genotype in the -318C/T polymorphism was absent and the predominant genotype was CC, while the predominant genotype for the +49A/G SNP was AA. As only few studies in this field have assessed Iranian and even Middle Eastern populations, additional studies with a higher number of samples are recommended to further assess the impact of -318C/T (rs5742909) and +49A/G (rs231775) polymorphisms of CTLA-4 on HT.

The interaction between genetic factors, blood glucose and hypertension plays a role in the onset of diabetic kidney disease (DKD) in type II diabetes mellitus (T2DM). Genetic variation of TGF-ß1 is associated with renal complication in T2DM with varying results between ethnicities. The Jambi Malay ethnic, which is the majority ethnic in Jambi Province, is an area that reports an increased prevalence of T2DM with DKD as the most frequent microvascular complications. In addition, previous study reported controlling blood glucose not associated with DKD indicating genetic may have play a role in DKD in this population. Studies related to genetic variation and decreased kidney function in T2DM patients has never been performed in this ethnic group. This study aimed to investigate the role of TGF-ß genetic variation as risk factor for decreased renal function in T2DM patients from Jambi Malay ethnicity. We conducted a cross sectional study involving 70 patients with T2DM. The inclusion criteria for renal complication based on a decrease in the glomerular filtration rate (GFR) of less than 60 mL/min/1.73. The genotyping method used was amplification refractory mutation system polymerase chain reaction (ARMS-PCR) for TGF-β1 rs1800470 T/C. Bivariate and multivariate analysis was performed to analyze phenotype and genotype association. The result of bivariate analysis showed T2DM patients with genotype CT (p:0.006; OR:0.125; 95% CI:0.027-0.575) and CC (p:0.007; OR:0.104; 95% CI:0.020-0.546) or C allele carrier (p:0.003; OR:0.117; 95% CI:0.027-0.500) had lower risk for decreased renal function than TT genotype. Multivariate analysis that included blood pressure and age variables showed the same finding for CT (p:0.007; OR:0.086; 95% CI:0.014-0.508) and CC genotype (p:0.022; OR:0.115; 95% CI:0.018-0.731). It is concluded from this study that T2DM patients with genotype CT, CC and carrier allele C have a lower risk for suffering kidney complications than genotype TT.

The present study aimed to investigate the correlation between cystathionine β-synthase (CBS) T833C polymorphisms and primary hypertension. A case-control study was conducted by genotyping the representative variation in 545 hypertensive individuals (aged 49.23±7.56 years) and 500 normotensive individuals (aged 49.90±10.01 years). The T833C genetic polymorphisms of the CBS enzyme were detected in all subjects by amplification refractory mutation system polymerase chain reaction (PCR) analysis. The CBS T833C polymorphism was successfully genotyped in the general population with a sample size of 1,045 (545+500) individuals. The genotypic and allelic frequency distributions of the CBS T833C polymorphism were not significantly different between the hypertensive and normotensive groups (P>0.05). The CC genotype was significantly different (P<0.05) from the CT and TT genotypes in terms of body mass index (BMI), and the levels of triglycerides (TG) and homocysteine (Hcy). Multiple logistic regression analysis revealed that BMI, total cholesterol (TC) level, smoking, plasma Hcy level and a family history of hypertension were the independent risk factors for hypertension in the population studied. The results indicate that the level of plasma Hcy was a risk factor for hypertension in the population studied. However, the mutation of the CBS T833C gene was not concluded to be an important hereditary factor for influencing the level of plasma Hcy.

Rheumatoid arthritis (RA) is a heterogeneous autoimmune disease, characterized by chronic inflammation, hyperplasia (swelling), tenderness, erosion of cartilage and bones in synovial joints. Transforming growth factor-β1 (TGF-β1) is an important regulator of inflammation, and its polymorphism is implicated in several diseases. Therefore, the study was done to determine whether TGF-β1 C/T gene polymorphism was associated with RA in North Indian population. Eighty-seven (male/female: 29/58) healthy controls and 76 (male/female: 17/59) RA patients were recruited for association study between TGF-β1 +869C/T polymorphism. TGF-β1 +869C/T polymorphism was genotyped by allele specific amplification refractory mutation system polymerase chain reaction (ARMS-PCR) to test susceptibility to clinical presentation of RA patients in North Indian population by comparing RA genotypes with control groups. The genotypic association studies and dominant, recessive, and allelic models revealed that TGF-β1 +869C/T gene polymorphism is involved in the onset of RA. TGF-β1 +869 T (either TT or CT) allele and TT v/s CC (OR = 36.18, 95% CI = 11.98-109.31, P = 0.001); TT + CT v/s CC (OR = 0.16, 95% CI = 0.08-0.33, P = 0.001); TT v/s CC + CT (OR = 0.04, 95% CI = 0.1-0.09, P = 0.001); and T v/s C (OR = 0.12, 95% CI = 0.07-0.2, P = 0.001) show significant association with RA as compared with CC genotype or C alleles (P = 0.001). The patient carrying T alleles showed significant associations with increased ESR, uric acid, CRP, DAS28-ESR, and number of tender joints as compared to other genotypes. In the presence of RF, DAS-28-ESR was high in CT genotype. ESR, CRP, and swollen joint count were highest in TT genotype of RF negative patients. TGF-β1 polymorphism is associated with disease activity of RA. Disease activity is strongly modulated in the presence of serum RF and TGF-β1 polymorphism. Key Points •TGF-β1 +869C/T polymorphism was found to be associated with RA in the patients. •The polymorphism showed significant association with all inflammatory parameters as ESR, CRP, and DAS-28 in RA subjects. •RF negative patients showed high ESR, CRP, and swollen joint count with TT genotype. •TGF-β1 polymorphism and serum RF are modulating disease activity in RA.

Coronavirus disease (COVID-19) is an acute infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human SP-D (surfactant protein D) is known to interact with the spike protein of SARS-CoV, but its immune surveillance against SARS-CoV-2 is not known. The current study aimed to examine the potential of a recombinant fragment of human SP-D (rfhSP-D) as an inhibitor of replication and infection of SARS-CoV-2. The interaction of rfhSP-D with the spike protein of SARS-CoV-2 and human ACE-2 (angiotensin-converting enzyme 2) receptor was predicted via docking analysis. The inhibition of interaction between the spike protein and ACE-2 by rfhSP-D was confirmed using direct and indirect ELISA. The effect of rfhSP-D on replication and infectivity of SARS-CoV-2 from clinical samples was assessed by measuring the expression of RdRp gene of the virus using quantitative PCR. In silico interaction studies indicated that three amino acid residues in the receptor-binding domain of spike protein of SARS-CoV-2 were commonly involved in interacting with rfhSP-D and ACE-2. Studies using clinical samples of SARS-CoV-2–positive cases (asymptomatic, n = 7; symptomatic, n = 8) and negative control samples (n = 15) demonstrated that treatment with 1.67 μM rfhSP-D inhibited viral replication by ∼5.5-fold and was more efficient than remdesivir (100 μM) in Vero cells. An approximately two-fold reduction in viral infectivity was also observed after treatment with 1.67 μM rfhSP-D. These results conclusively demonstrate that the rfhSP-D mediated calcium independent interaction between the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike protein and human ACE-2, its host cell receptor, and significantly reduced SARS-CoV-2 infection and replication in vitro.

Dental caries is a complex condition that results from a combination of genetic and environmental factors. Several genes have been found to play a role in teeth development and have been associated with various dental traits. In this study, our objective was to examine the potential correlation between the ectodysplasin a receptor (EDAR)-associated via death domain (EDARADD), Lactoperoxidase (LPO) and Actinin Alpha 2 (ACTN2) gene polymorphisms and susceptibility to dental caries. The study included a total of 600 participants, comprising 300 individuals with dental caries and 300 caries-free controls. The genotyping of the EDARADD (rs79233817), LPO (rs8178275) and ACTN2 (rs114880747) gene polymorphisms was performed using the tetra-primer amplification refractory mutation system Polymerase chain reaction (PCR) method. Individuals with dental caries were found to have a significantly higher frequency of the A allele (minor allele) for rs79233817 compared to controls. The specific single nucleotide polymorphism (SNP) (rs79233817) was associated with an increased risk of dental caries (DC) in both the co-dominant and dominant genetic models (p-value < 0.05). In addition, the study's findings revealed a significant association between the rs114880747 SNP and susceptibility to dental caries (p-value < 0.05). A higher frequency of the A allele (minor allele) of rs114880747 was observed in patients compared to the healthy controls. It is also worth mentioning that there was no association between rs8178275 susceptibility to dental caries (p-value > 0.05). It can be inferred that the EDARADD gene polymorphism (rs79233817) and ACTN2 gene polymorphism (rs114880747) potentially play a role in the genetic susceptibility to dental caries. To validate and delve deeper into these findings, it is necessary to conduct additional studies with larger sample sizes in diverse populations. This will help to establish the robustness of the results and further investigate the underlying mechanisms involved.

BackgroundThe rs2282679 polymorphism in the vitamin D binding protein (DBP) gene may influence the response to vitamin D supplementation. Therefore, we examine the effect of 1-year vitamin D supplementation on vitamin D deficiency (VDD) with the interaction of rs2282679 polymorphism in overweight and obese children and adolescents.Materials and methodsThe participants (n = 300) were part of a randomized controlled trial who received a daily supplement of either 1,000 or 2,000 IU or four supplements of 1,000 IU weekly (equal to 600 IU daily) of vitamin D3 for 12 months. Genotyping was performed using amplification refractory mutation system polymerase chain reaction (ARMS-PCR).ResultsThe mean of 25(OH)D values at baseline for participants with the TT, TG, and GG genotypes were 15.4, 14.4, and 10.8 ng/mL, respectively, and were not different between the three genotype groups (P = 0.062). A significant reduction in VDD was observed after vitamin D supplementation with dosages of 1,000 or 2,000 IU compared to 600 IU. No significant association of genotypes with risk of VDD was observed in each intervention group after vitamin D supplementation, except, that individuals with TG genotype showed a higher risk of VDD compared to those with TT genotype in the 2,000 IU group after 6 months of supplementation [odds ratio (95% CI): 6.94; 1.30–37.02]. We observed no interaction between time duration, three genotypes, and dosages with serum 25(OH)D, calcium, phosphorus, alkaline phosphatase, and parathyroid hormone levels.ConclusionResponse to vitamin D supplementation by three doses of 600, 1,000, and 2,000 IU could not be affected by rs2282679 polymorphism during 12 months in overweight and obese children and adolescents.

Hypertrophic cardiomyopathy (HCM) is a common and complex, genetically inherited, cardiovascular disorder. It is typically inherited in an autosomal dominant manner with variable penetrance and mutable expression. Mutations in MYBPC3 gene is one of the genetic causes of HCM. Only 0.2% of general population suffers from HCM. The MYBPC3 gene provides instructions for making cardiac myosin binding protein C, which is imperative for the maintenance and regulation of normal cardiac functions. This study aims to explore the reported SNP rs1052373 from exon 30 of MYBPC3 gene in the population of Punjab, Pakistan. The reported SNP rs1052373 was analysed using Tetra Amplification Refractory Mutation System Polymerase Chain Reaction (T-ARMS-PCR) to find the allelic frequency in the selected population. T-ARMS-PCR is a cost effective, flexible, rapid, and accurate tool for genotyping. The specific sequences of MYBPC3 gene from exons 30 and 31 and introns 29, 30, and 31 were retrieved from NCBI (https://www.ncbi.nlm.nih.gov/). A tetra primer designing tool known as Primer 1 (http://primer1.soton.ac.uk/primer1.html) was used to design the primers for the targeted region of MYBPC3 gene. In this study, the genotyping of previously reported SNP rs1052373 showed variation in the disease group, giving CC, CT, and TT genotypes with the frequency of 0.04. The genotyping analysis of rs1052373 showed that the allelic frequency of homozygous condition T/T was 0.02 and the allelic frequency of heterozygous condition C/T was 0.02 in disease group as compared to the control group. In the latter, the homozygous T/T and heterozygous C/T genotypes were not observed in any individuals. All the individuals in control group carried homozygous C/C genotype. While, the frequency of homozygous C/C genotype was 0.96 in disease group. The findings of this study would help to find novel molecular markers for HCM diagnosis.

Background:Blighted ovum is one of the most common reasons for abortion during the first three months of pregnancy. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme in the human immune system. The gene is located on 6q25 chromosome and acts on mitochondrial matrix. In the case of mutation or inactivity of this enzyme, mitochondrial and nuclear DNA will severely be destructed. The most common polymorphism of its gene is Val16Ala.Objective:The aim was to investigate a possible mutation in pregnant women who had abortion during the first trimester of pregnancy due to blighted ovum.Materials and Methods:In this case-control study, 34 women were entered as the case and control groups, respectively. Genome DNA was extracted from saliva samples and its genotype was determined using Tetra-primer amplification refractory mutation system polymerase chain reaction technique. Results:In the case group, 16 (48%) cases had Val/Val genotype, 17 (50%) were heterozygote and had Val/Ala genotype, and 1 (2%) had Ala/Ala genotype. Among controls, 7 (22%) items had Val/Val genotype, 6 (17%) had Val/Ala genotype, and 21 (61%) had Ala/Ala genotype. The frequency of TT, CT, and CC genotypes was 48%, 50%, and 2% in case group and 22%, 17%, and 61% in control group, respectively. Statistical analysis revealed a significant relationship between Val16Ala polymorphism of MnSOD gene and blighted ovum (p= 0.0003).Conclusion: It has concluded that a significant relationship exists between Val16Ala polymorphism of MnSOD gene and blighted ovum.