The Egyptian journal of medical human genetics最新文献

Background: The association between cocaine- and amphetamine-regulated transcript prepropeptide gene (CARTPT) and obesity-related outcomes has shown in the epidemiological studies. Nevertheless, there is lack of data regarding the CARTPT gene-diet interactions in terms of antioxidant potential of diet. So, this study aimed to test CARTPT gene-dietary non-enzymatic antioxidant capacity (NEAC) interactions on cardio-metabolic risk factors in obese individuals.

Methods and material: The present cross-sectional study was carried out among 288 apparently healthy obese adults within age range of 20-50 years. Antioxidant capacity of diet was estimated by calculating the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total radical-trapping antioxidant parameter (TRAP) and Trolox equivalent antioxidant capacity (TEAC) using a semiquantitative food frequency questionnaire (FFQ). Genotyping for CARTPT rs2239670 polymorphism was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results: A significant interaction was revealed between CARTPT rs2239670 and dietary ORAC on BMI (P_Interaction = 0.048) and fat mass percent (FM%) (P_Interaction = 0.008); in A allele carriers, higher adherence to the dietary ORAC was related to lower level of BMI and FM%. And, the significant interactions were observed between FRAP index and rs2239670 in relation to HOMA (P_Interaction = 0.049) and QUICKI (P_Interaction = 0.048). Moreover, there were significant interactions of rs2239670 with TRAP (P_Interaction = 0.029) and TEAC (P_Interaction = 0.034) on the serum glucose level; individuals with AG genotype were more respondent to higher intake of TRAP.

Conclusion: The present study indicated that the relationships between CARTPT rs2239670 and obesity and its-related metabolic parameters depend on adherence to the dietary NEAC. Large prospective studies are needed to confirm our findings.

Background: Blood group has been stated to be one of the risk factors associated with viral diseases like dengue, hepatitis virus, Norwalk virus and even the coronavirus associated with 2003 severe acute respiratory syndrome (SARS) outbreak. In addition, anti-A antibodies in experimental models have been shown to inhibit the interaction between coronavirus and angiotensin converting enzyme (ACE) receptor of the host target cell, the major receptor involved in viral pathogenesis. Thus, several workers propose an association between ABO blood type and coronavirus disease- 2019 (COVID-19) disease in many previous studies. The present study was undertaken in the Eastern part of India in line with these authors to study the association of ABO blood group of patients with COVID susceptibility and severity.

Methods: This is a retrospective study over a period of 6 months from June 2020 to November 2020 where patients who underwent quantitative real-time polymerase chain reaction (qRT-PCR) test for SARS-COV2 and having a recorded patient blood group type were considered. The qRT-PCR positive admitted cases were considered as cases, and qRT-PCR negative cases were considered as controls. Data were entered in Microsoft Excel format and analyzed by statistical method to obtain association.

Results: Consecutively obtained 5000 qRT-PCR positive patients (cases) and 11,700 (controls) were included in the present study. The mean age of cases was higher (54.24 vs. 34. 67) than the controls. Among the cases, the highest number (2379; 47.6%) of samples belonged to A blood group followed by B (1278; 25.6%) while among the control group O blood group had the highest prevalence (4215; 36%). Blood group A had a higher odd of testing positive (Odds ratio-2.552; CI 2.381-2.734; p < 0.0001) than all other blood groups. A blood group is also associated with higher risk of ICU admission (Odds ratio- 1.699; 95% CI 1.515-1.905) and 65.3% of this group is also associated with high viral load which gives an indication of higher disease severity.

Conclusion: Blood group A is associated with an increased susceptibility to COVID 19 infection than other blood groups. Cases of this blood group are also associated with more critical care needs and a higher viral load on testing.

Background: Union between second cousins and closer relatives is called consanguineous marriage. Consanguineous marriage is associated with increased risk of autosomal recessive diseases and several multifactorial traits. In order to evaluate the association between prevalence/mortality of COVID-19 and the frequency of consanguineous marriage, the present ecologic study was carried out. For the present study, data of prevalence (per 10⁶ people) and mortality (per 10⁶ people) and number of performed laboratory diagnostic test (per 10⁶ people) of COVID-19 disease at four time points (December 2020; March, August and October 2021) of 65 countries were used.

Results: Univariable correlation and generalized estimating equation analysis were used. In analysis, prevalence and mortality of COVID-19 were used as dependent variables and human development index, number of performed diagnosis test and the mean of inbreeding coefficient (α-value) were introduced into model as covariates, and time point was used as a factor in analysis. The square root (SR) of prevalence (P = 0.008) and SR-mortality (P < 0.001) of COVID-19 negatively associated with the log-transformed of α-value.

Conclusions: The present finding means that in countries with high levels of consanguineous marriages, the prevalence of COVID-19 and mortality due to COVID-19 were lower than countries having low level of marriage with relatives.

In December 2019, a novel respiratory tract infection, from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in China that rapidly spread around the world. This virus possesses spike (S) glycoproteins on the surface of mature virions, like other members of coronaviridae. The S glycoprotein is a crucial viral protein for binding, fusion, and entry into the target cells. Binding the receptor-binding domain (RBD) of S protein to angiotensin-converting enzyme 2 (ACE 2), a cell-surface receptor, mediates virus entry into cells; thus, understanding the basics of ACE2 and S protein, their interactions, and ACE2 targeting could be a potent priority for inhibition of virus infection. This review presents current knowledge of the SARS-CoV-2 basics and entry mechanism, structure and organ distribution of ACE2, and also its function in SARS-CoV-2 entry and pathogenesis. Furthermore, it highlights ACE2 targeting by recombinant ACE2 (rACE2), ACE2 activators, ACE inhibitor, and angiotensin II (Ang II) receptor blocker to control the SARS-CoV-2 infection.

Background: Non-communicable diseases such as cardiovascular diseases, respiratory diseases and diabetes contribute to the majority of deaths in India. Public health programmes on non-communicable diseases (NCD) prevention primarily target the behavioural risk factors of the population. Hereditary is known as a risk factor for most NCDs, specifically, type 2 diabetes mellitus (T2DM), and hence, understanding of the genetic markers of T2DM may facilitate prevention, early case detection and management.

Main body: We reviewed the studies that explored marker-trait association with type 2 diabetes mellitus globally, with emphasis on India. Globally, single nucleotide polymorphisms (SNPs) rs7903146 of Transcription Factor 7-like 2 (TCF7L2) gene was common, though there were alleles that were unique to specific populations. Within India, the state-wise data were also taken to foresee the distribution of risk/susceptible alleles. The findings from India showcased the common and unique alleles for each region.

Conclusion: Exploring the known and unknown genetic determinants might assist in risk prediction before the onset of behavioural risk factors and deploy prevention measures. Most studies were conducted in non-representative groups with inherent limitations such as smaller sample size or looking into only specific marker-trait associations. Genome-wide association studies using data from extensive prospective studies are required in highly prevalent regions worldwide. Further research is required to understand the singular effect and the interaction of genes in predicting diabetes mellitus and other comorbidities.

Background: We present a case of alpha-fucosidosis, a lysosomal storage disorder, from Egypt. The report also includes a brief review of the COVID-19 and lysosomal storage diseases relationship.

Case presentation: A female patient aged 18 years, diagnosed with type II fucosidosis, based on the cutaneous signs, characteristic facies, and systemic symptoms, and diagnosis was confirmed using genetic analysis. The patient died from COVID-19 pneumonia during the COVID-19 pandemic after getting the infection from her father and being hospitalized.

Conclusions: Patients with lysosomal storage diseases with local or systemic immune suppression may be predisposed to respiratory complications of COVID-19. Intense care with protective guidelines should be applied to those patients.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a significant public health challenge globally. SARS-CoV-2 is a novel virus, and the understanding of what constitutes expressed RNAseq variants in healthy, convalescent, severe, moderate, and those admitted to the intensive care unit (ICU) is yet to be presented. We characterize the different expressed RNAseq variants in healthy, severe, moderate, ICU, and convalescent individuals.

Materials and methods: The bulk RNA sequencing data with identifier PRJNA639275 were downloaded from Sequence Reads Archive (SRA). The individuals were divided into: (1) healthy, n = 34, moderate, n = 8, convalescent, n = 2, severe, n = 16, and ICU, n = 8. Fastqc version 0.11.9 and Cutadapt version 3.7 were used to assess the read quality and perform adapter trimming, respectively. STAR was used to align reads to the reference genome, and GATK best practice was followed to call variants using the rnavar pipeline, part of the nf-core pipelines.

Results: Our analysis demonstrated that different sets of unique RNAseq variants characterize convalescent, moderate, severe, and those admitted to the ICU. The data show that the individuals who recover from SARS-CoV-2 infection have the same set of expressed variants as the healthy controls. We showed that the healthy and SARS-CoV-2-infected individuals display different sets of expressed variants characteristic of the patient phenotype.

Conclusion: The individuals with severe, moderate, those admitted to the ICU, and convalescent display a unique set of variants. The findings in this study will inform the test kit development and SARS-CoV-2 patients classification to enhance the management and control of SARS-CoV-2 infection in our population.

Background: Since the COVID-19 outbreak emerged, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved into variants with underlying mutations associated with increased transmissibility, potential escape from neutralizing antibodies, and disease severity. Although intensive research is ongoing worldwide to understand the emergence of SARS-CoV-2 variants, there is a lack of information on what constitutes the expressed RNA variants in critical and non-critical comorbidity-free young patients. The study sought  to characterize the expressed RNA variants from young patients with critical and non-critical forms of SARS-CoV-2 infection.

Methodology: The bulk ribonucleic acid (RNA) sequencing data with the identifier GSE172114 were downloaded from the Gene Expression Omnibus (GEO) database. The study participants were divided into critical, n = 46, and non-critical, n = 23. FastQC version 0.11.9 and Cutadapt version 3.7 were used to assess the read quality and perform adapter trimming, respectively. Spliced Transcripts Alignment to a Reference (STAR) version 2.7.10a was used to align reads to the human (hg38) reference genome. Genome Analysis Tool Kit (GATK) best practice was followed to call variants using the rnavar pipeline, part of the nf-core pipelines.

Results: Our research demonstrates that critical and non-critical SARS-CoV-2-infected individuals are characterized by a unique set of expressed RNA variants. The expressed gene variants are enriched on the innate immune response, specifically neutrophil-mediated immune response. On the other hand, the expressed gene variants are involved in both innate and cellular immune responses.

Conclusion: Deeply phenotyped comorbidity-free young patients with critical and non-critical SARS-CoV-2 infection are characterized by a unique set of expressed RNA variants. The findings in this study can inform the patient classification process in health facilities globally when admitting young patients infected with SARS-CoV-2.

The SARS-CoV-2 has infected many people globally with the ravaging COVID-19; a disease, which has become challenging for every aspect of modern healthcare. The saliva and oral mucosa are sites of high risk for increased viral loads, and aside from the usual epithelial functions like lining and protection, the oral mucosa is also specialized for crucial functions, such as secretion, mastication, sensory perception, and taste perception. The human ACE2 receptor has been extensively studied for its essential role in the regulation of blood pressure homeostasis. However, scRNA-Seq studies have revealed high expression levels of the protein in keratinized epithelial surfaces of the oral cavity. The SARS-CoV-2 have access to the host's body by binding to the ACE2 receptor, leading to the cleavage and major conformational changes in the viral spike glycoprotein for the release of its nucleocapsid into the cellular cytoplasm. This proteolytic cleavage is carried out by the TMPRSS2 and cathepsin L. In this study, we harnessed the information from the binding interface of TMPRSS2 and PAI-1 (a protease inhibitor known to inhibit the TMPRSS2 and several other proteases) to design a potential therapeutic peptide for the inhibition of the TMPRSS2, while also emphasizing the need for preventive masking.

Supplementary information: The online version contains supplementary material available at 10.1186/s43042-022-00213-z.

Background: Diagnosis of tuberculosis (TB) in the era of technological sophistication requires accuracy and speed to provide as much information as possible so that TB treatment can be carried out quickly and precisely. New studies have also begun to be carried out to diagnose TB, one of which is by examining genes, either by looking at polymorphisms, mutations, or expressions. Several previous studies have confirmed the association of MC3R and TB genes with polymorphisms; MC3R is a gene that participates in the regulation of the inflammatory process and is also found in macrophages; therefore, we tried to analyze gene expression in the active TB group, household contacts, and healthy controls for looked at the differences between the three groups and confirmed the correlation of MC3R with TB by seeing which group's gene expression increased the most expression of the three groups so that the results can be considered as a TB diagnostic biomarker in the future.

Methods: This study included 122 people, 49 patients with confirmed TB, 46 close relatives of patients, and 27 healthy controls. This study used a real-time PCR technique to analyze MC3R gene expression in the three groups, and all data were analyzed using Bio-Rad CFXTM software version 3.1 and one-way ANOVA using SPSS 21.0.

Results: The value of MC3R gene expression in the active TB group increased 3.6-fold in the healthy group (p = 0.143), and that of gene expression in the healthy control group increased 1.09-fold in the healthy group (p = 0.007).

Conclusion: There is a relationship between MC3R and TB based on the results of gene expression analysis that increased in the active TB group compared to the household contact group and healthy controls.