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.

Keywords: Arab; Disease association; HLA; MHC.

Fig. 1

Proportions of ancestral genomes that have accumulated in the contemporary population of the UAE. Data was obtained from the genome wide analysis study of 1000 UAE citizens which provide insights into the admixture of the contemporary population. The main ancestral contribution can be traced back to South Asia (27%) which can be explained by a history of trade and exchange between the regions (Tay et al. 2020)

Fig. 2

Histogram showing the distribution of variants number at chromosome 6 with troughs (low variability) and peaks (high variability) (Tay et al. 2020). Data were obtained from a genome wide association studies on 1,000 UAE citizens. Unsurprisingly, there is a significant peak in the number of variants on the short arm of chromosome 6, specifically around the MHC region. The MHC contains gene families with variable copy numbers. The size of MHC haplotypes can vary according to the gene copy number around the HLA class II and C4/CYP21 regions. The table shows the different gene copy numbers in different MHC ancestral haplotypes (Zhang et al. 1990)