Since the discovery of human leukocyte antigens (HLAs), the function of major histocompatibility complex (MHC) gene families in a wide range of diseases have been the subject of research for decades. In particular, the associations of autoimmune disorders to allelic variants and candidate genes encoding the MHC are well documented. However, despite decades of research, the knowledge of MHC associations with human disease susceptibility have been predominantly studied in European origin, with limited understanding in different populations and ethnic groups. This is particularly evident in countries and ethnic populations of the Arabian Peninsula. Human MHC haplotypes, and its association with diseases, of the variable ethnic groups of this region are poorly studied. This review compiled published manuscripts that have reported a list of autoimmune diseases (insulin-dependent diabetes mellitus, systemic lupus erythematosus, myasthenia gravis, rheumatoid arthritis, psoriasis vulgaris, and multiple sclerosis) associated with MHC class I and class II in the populations of the Arabian Peninsula, specifically Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, the United Arab Emirates, and Yemen. Data available was compared with other three ethnic groups, namely Caucasians, Asians, and Africans. The limited data available in the public domain on the association between MHC gene and autoimmune diseases highlight the challenges in the Middle Eastern region.
The high degree of polymorphism of the HLA system provides suitable genetic markers to study the diversity and migration of different world populations and is beneficial for forensic identification, anthropology, transplantation and disease associations. Although the United Arab Emirates (UAE) population of about nine million people is heterogeneous, information is limited for the HLA class I allele and haplotype frequencies of the Bedouin ethnic group. We performed low‐resolution PCR‐SSP genotyping of three HLA class I loci at HLA‐A, ‐B and ‐C for 95 unrelated healthy Bedouins from the cities of Al Ain and Abu Dhabi in the UAE. A total of 54 HLA allele lineages were detected; the most frequent low‐resolution allele lineages at each HLA locus were A*02 (0.268), B*51 (0.163) and C*07 (0.216). The inferred estimates for the two most frequent HLA‐A and HLA‐B haplotypes were HLA‐A*02 ~ HLA‐B*50 (0.070) and HLA‐A*02 ~ HLA‐B*51 (0.051), and the most frequent 3‐locus haplotype was HLA‐A*02 ~ HLA‐B*50 ~ HLA‐C*06 (0.068). The HLA allele lineage frequencies of the UAE Arabs were compared to those previously reported for 70 other world populations, and a strong genetic similarity was detected between the UAE Arabs and the Saudi Arabians from the west with evidence of a limited gene flow between the UAE Arabs and Pakistani across the Gulf from the east, and the UAE Arabs and Omani from the south of the Gulf Peninsula.
Polymorphic Alu insertions (POALINs) are found throughout the human genome and have been used in various studies to infer geographic origin of human populations. The main aim of this study was to determine the allele and haplotype frequencies of five POALINs, AluHF, AluHG, AluHJ, AluTF and AluMICB, within the major histocompatibility complex (MHC) class I region of 95 UAE Arabs, and correlate their frequencies to those of the HLA‐A, HLA‐C and HLA‐B class I allele lineages. Evolutionary relationships between the POALINs of the Arabs and those previously studied in populations of African, Asian and European descent were compared. At each of the five Alu loci (AluHF, AluHG, AluHJ, AluTF and AluMICB), Alu insertion was designated as Alu(locus)*02 and absence was Alu(locus)*01. The AluHG insertion (AluHG*02) had the highest frequency (0.332), followed by AluHF*02 (0.300), AluHJ*02 (0.263), AluMICB*02 (0.111) and AluTF*02 (0.058). Of the 270 Alu‐HLA haplotypes pairs in the UAE Arabs, 110 had no Alu insertion, and 54 had an Alu insertion at >50% per haplotype. An Alu insertion >75% per haplotype was found between AluMICB*02 and HLA‐B*14, HLA‐B*22, HLA‐B*44, HLA‐B*55, HLA‐B*57 and HLA‐B*73, and with HLA‐C*01 and HLA‐C*18; AluHJ*02 with HLA‐A*01, HLA‐A*19, HLA‐A*24 and HLA‐A*32; AluHG*02 with HLA‐A*02 and HLA‐B*18; and AluHF*02 with HLA‐A*10. The genotyped allele and haplotype frequencies of the MHC POALINs in UAE Arabs were compared with the results of 30 previously published Asian, European, American and African populations. Phylogenetic and multidimensional scaling (MDS) analysis of the relative MHC POALINs allele and haplotype frequencies revealed that the UAE Arabs have a similar lineage to Caucasians and the most distant genetic relationship to the Waorani native American population of Ecuador. The structure of both the phylogenetic tree and the MDS analysis supports the Out of Africa theory of human evolution. The nature of the clusters suggests the Arabian Middle East represents a crossroads from which human populations migrated towards Asia in the east and Europe to the north‐west.
This is the first study to report the diversity of a population of the Arabian Peninsula using 27 Y-STR. MDS plots show that Middle Eastern populations are positioned in the centre, with African, Asian and European populations around the Arab population cluster. The findings of this study are consistent with this region being at the epicentre of human migration between continents.
Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N) by chemical reaction when it reacts with hydrogen peroxide (HO), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of HO. HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.