Major histocompatibility complex (MHC) associations with diseases in ethnic groups of the Arabian Peninsula

Abstract

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.

Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

“…Given that the non-Qatari Middle Eastern group comprises nationals from Egypt, Sudan, Syria, Iran, and Yemen ( Table S5 ), it seems possible that genetic differences between the Qatari and non-Qatari Middle Eastern groups might underpin the apparently decreased magnitude of humoral responses following infection and increased risk of COVID-19 disease observed here for the Qatari group. While we did not have access to genome sequence data for this cohort to verify this, it is perhaps relevant that the Qatari population has been reported to have an elevated prevalence of common adult diseases [ 38 ], as well as of childhood autoimmune diseases such as type 1 diabetes [ 39 ], potentially suggestive of uncharacterized genetic factors that affect humoral immune responses through HLA allelic variation [ 40 ].…”

Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

“…MHC-I region contains a large number of immune-related genes, which are often polymorphic and closely linked as a result of their genomic proximity ( 6 ). In addition, many of these genes are associated with infections and autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ( 6 ).…”

“…MHC-I region contains a large number of immune-related genes, which are often polymorphic and closely linked as a result of their genomic proximity ( 6 ). In addition, many of these genes are associated with infections and autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) ( 6 ). The human MHC-I genomic region locates on chromosome 6p21.33-6p22.2, known as human leukocyte antigen (HLA) class I region which contains HLA gene loci and several non-HLA gene clusters ( 7 ).…”

Segregation Analysis of Genotyped and Family-Phased, Long Range MHC Classical Class I and Class II Haplotypes in 5 Families With Type 1 Diabetes Proband in the United Arab Emirates

“…Patients of Arabian ancestry share several MHC haplotypes which confer either susceptibility or protection to T1D with other ethnic groups ( Al Naqbi et al, 2021 ). However, there are also other disease-associated MHC haplotypes in Arabs that are distinct from other ethnic groups.…”

“…HLA-DR3 and HLA-DR4 appears the most common subtypes in T1D disease association studies involving Arabian populations ( Al-Hussein et al, 2003 ; Al-Harbi et al, 2004 ; Al-Jenaidi et al, 2005 ; Al-Herbish et al, 2008 ). However, there are a number of ethnic specific differences ( Al Naqbi et al, 2021 ). Of note, a study by Hajjej et al (2018) reported that HLA-DRB1 ∗ 03/HLA-DRB1 ∗ 04 genotype showed the highest risk of T1D development ( Hajjej et al, 2018 ).…”