HLA pharmacogenetic markers of drug hypersensitivity from the perspective of the populations of the Greater Middle East

Specific HLA associations with drug hypersensitivity may vary between geographic regions and ethnic groups. There are little to no data related to HLA-drug hypersensitivity on populations who reside in the Greater Middle East (GME), a vast region spanning from Morocco in the west to Pakistan in the east. In this review, the authors intended to summarize the significant HLA alleles associated with hypersensitive drug reactions induced by different drugs, as have been found in different populations, and to summarize the prevalence of these alleles in the specific and diverse populations of the GME. For example, HLA-B * 57:01 allele prevalence, associated with abacavir-induced hypersensitivity, ranges from 1 % to 3 %, and HLA-DPB1 * 03:01 prevalence, associated with aspirin-induced asthma, ranges from 10 % to 14 % in the GME population. Studying pharmacogenomic associations in the ethnic groups of the GME may allow the discovery of new associations, confirm ones found with a low evidence rate and enable cost-effectiveness analysis of allele screening before drug use

Recent Progress in Metal-Organic Framework-Derived Chalcogenides (MX; X = S, Se) as Electrode Materials for Supercapacitors and Catalysts in Fuel Cells

Supercapacitors (SCs) are recognized by high power densities and significantly higher cyclic stability compared to batteries. However, the energy density in SCs should be improved for better applications and commercialization. This could be achieved by developing materials characterized by such porous structures as metal-organic frameworks (MOFs) and metal chalcogenides in the electrodes’ materials. Herein, the recent advances in MOF derived from metal sulfides and selenides as electrode materials for SCs are reviewed and discussed. Strategies such as adopting core-shell structures, carbon-coating, and doping, which are used to promote the electrochemical performances of these MOF-based materials, are presented. Additionally, the progress in developing S-doped MOF-derived catalysts for the oxidation-reduction reaction (ORR) in the cathode of fuel cells is also reviewed. In addition, the challenges and future research trends are summarized in this minireview

Characterizing the diversity of MHC conserved extended haplotypes using families from the United Arab Emirates

Aside from its anthropological relevance, the characterization of the allele frequencies of genes in the human Major Histocompatibility Complex (MHC) and the combination of these alleles that make up MHC conserved extended haplotypes (CEHs) is necessary for histocompatibility matching in transplantation as well as mapping disease association loci. The structure and content of the MHC region in Middle Eastern populations remain poorly characterized, posing challenges when establishing disease association studies in ethnic groups that inhabit the region and reducing the capacity to translate genetic research into clinical practice. This study was conceived to address a gap of knowledge, aiming to characterize CEHs in the United Arab Emirates (UAE) population through segregation analysis of high-resolution, pedigree-phased, MHC haplotypes derived from 41 families. Twenty per cent (20.5%) of the total haplotype pool derived from this study cohort were identified as putative CEHs in the UAE population. These consisted of CEHs that have been previously detected in other ethnic groups, including the South Asian CEH 8.2 [HLA- C*07:02-B*08:01-DRB1*03:01-DQA1*05:01-DQB1*02:01 (H.F. 0.094)] and the common East Asian CEH 58.1 [HLA- C*03:02-B*58:01-DRB1*03:01- DQA1*05:01-DQB1*02:01 (H.F. 0.024)]. Additionally, three novel CEHs were identified in the current cohort, including HLA- C*15:02-B*40:06-DRB1*16:02-DQB1*05:02 (H.F. 0.035), HLA- C*16:02-B*51:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.029), and HLA- C*03:02-B*58:01-DRB1*16:01-DQA1*01:02-DQB1*05:02 (H.F. 0.024). Overall, the results indicate a substantial gene flow with neighbouring ethnic groups in the contemporary UAE population including South Asian, East Asian, African, and European populations. Importantly, alleles and haplotypes that have been previously associated with autoimmune diseases (e.g., Type 1 Diabetes) were also present. In this regard, this study emphasizes that an appreciation for ethnic differences can provide insights into subpopulation-specific disease-related polymorphisms, which has remained a difficult endeavour

Investigating the genetic makeup of the major histocompatibility complex (MHC) in the United Arab Emirates population through next-generation sequencing

Abstract The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the HLA alleles was achieved through the application of the bioinformatics tools, HLA-LA and xHLA. Subsequently, the findings from this study were compared with other local and international datasets. A broad range of HLA alleles in the UAE population, of which some were previously unreported, was identified. A comparison with other populations confirmed the current population’s unique intertwined genetic heritage while highlighting similarities with populations from the Middle East region. Some disease-associated HLA alleles were detected at a frequency of > 5%, such as HLA-B*51:01, HLA-DRB1*03:01, HLA-DRB1*15:01, and HLA-DQB1*02:01. The increase in allele homozygosity, especially for HLA class I genes, was identified in samples with a higher level of genome-wide homozygosity. This highlights a possible effect of consanguinity on the HLA homozygosity. The HLA allele distribution in the UAE population showcases a unique profile, underscoring the need for tailored databases for traditional activities such as unrelated transplant matching and for newer initiatives in precision medicine based on specific populations. This research is part of a concerted effort to improve the knowledge base, particularly in the fields of transplant medicine and investigating disease associations as well as in understanding human migration patterns within the Arabian Peninsula and surrounding regions

Angiogenesis goes computational - The future way forward to discover new angiogenic targets?

Multi-omics technologies are being increasingly utilized in angiogenesis research. Yet, computational methods have not been widely used for angiogenic target discovery and prioritization in this field, partly because (wet-lab) vascular biologists are insufficiently familiar with computational biology tools and the opportunities they may offer. With this review, written for vascular biologists who lack expertise in com-putational methods, we aspire to break boundaries between both fields and to illustrate the potential of these tools for future angiogenic target discovery. We provide a comprehensive survey of currently avail-able computational approaches that may be useful in prioritizing candidate genes, predicting associated mechanisms, and identifying their specificity to endothelial cell subtypes. We specifically highlight tools that use flexible, machine learning frameworks for large-scale data integration and gene prioritization. For each purpose-oriented category of tools, we describe underlying conceptual principles, highlight interesting applications and discuss limitations. Finally, we will discuss challenges and recommend some guidelines which can help to optimize the process of accurate target discovery.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY-NC-ND license (http://creative-commons.org/licenses/by-nc-nd/4.0/)

HLA class I associations with the severity of COVID-19 disease in the United Arab Emirates.

SARS-CoV-2 appears to induce diverse innate and adaptive immune responses, resulting in different clinical manifestations of COVID-19. Due to their function in presenting viral peptides and initiating the adaptive immune response, certain Human Leucocyte Antigen (HLA) alleles may influence the susceptibility to severe SARS-CoV-2 infection. In this study, 92 COVID-19 patients from 15 different nationalities, with mild (n = 30), moderate (n = 35), and severe (n = 27) SARS-CoV-2 infection, living in the United Arab Emirates (UAE) were genotyped for the Class I HLA -A, -C, and -B alleles using next-generation sequencing (NGS) between the period of May 2020 to June 2020. Alleles and inferred haplotype frequencies in the hospitalized patient group (those with moderate to severe disease, n = 62) were compared to non-hospitalized patients (mild or asymptomatic, n = 30). An interesting trend was noted between the severity of COVID-19 and the HLA-C*04 (P = 0.0077) as well as HLA-B*35 (P = 0.0051) alleles. The class I haplotype HLA-C*04-B*35 was also significantly associated (P = 0.0049). The involvement of inflammation, HLA-C*04, and HLA-B*35 in COVID-19 severity highlights the potential roles of both the adaptive and innate immune responses against SARS-CoV-2. Both alleles have been linked to several respiratory diseases, including pulmonary arterial hypertension along with infections caused by the coronavirus and influenza. This study, therefore, supports the potential use of HLA testing in prioritizing public healthcare interventions for patients at risk of COVID-19 infection and disease progression, in addition to providing personalized immunotherapeutic targets

HLA repertoire of 115 UAE nationals infected with SARS-CoV-2

The class I and class II Human Leucocyte Antigens (HLA) are an integral part of the host adaptive immune system against viral infections. The characterization of HLA allele frequency in the population can play an important role in determining whether HLA antigens contribute to viral susceptibility. In this regard, global efforts are currently underway to study possible correlations between HLA alleles with the occurrence and severity of SARS-CoV-2 infection. Specifically, this study examined the possible association between specific HLA alleles and susceptibility to SARS-CoV-2 in a population from the United Arab Emirates (UAE). The frequencies of HLA class I (HLA-A, -B, and -C) and HLA class II alleles (HLA-DRB1 and -DQB1); defined using Next Generation Sequencing (NGS); from 115 UAE nationals with mild, moderate, and severe SARS-CoV-2 infection are presented here. HLA alleles and supertypes were compared between hospitalized and non-hospitalized subjects. Statistical significance was observed between certain HLA alleles and supertypes and the severity of the infection. Specifically, alleles HLA-B*51:01 and HLA-A*26:01 showed a negative association (suggestive of protection), whilst genotypes HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 showed a positive association (suggestive of predisposition) to COVID-19 severity. The results support the potential use of HLA testing to differentiate between patients who require specific clinical management strategies

Demographics data of the non-hospitalized and non-hospitalized SARS-CoV-2 infected patients.

Demographics data of the non-hospitalized and non-hospitalized SARS-CoV-2 infected patients.</p

HLA class I allele count and statistical association in non-hospitalized and hospitalized SARS-CoV2 infected patients.

Alleles that showed statistical significance (corrected P-value < 0.05) are highlighted. OR: Odds ratio, CI: confidence interval.</p