Zayed Hatem
College of Health Sciences, Biomedical Program, Qatar University, Doha, Qatar.
Curr Diab Rep. 2016 May;16(5):37. doi: 10.1007/s11892-016-0736-4.
Type 1 diabetes (T1D) is a complex autoimmune disorder that results from the T cell-mediated destruction of the pancreatic β cells and is due to interactions between environmental and genetic factors. Although Arabs have one of the highest global incidence and prevalence rates of T1D, unfortunately, there is a dearth of information regarding the genetic epidemiology of T1D in the Arab world. Arabs share several HLA haplotypes with other ethnic groups, which confer either susceptibility or protection to T1D, but they have specific haplotypes that are distinctive from other ethnicities. Among different Arab countries, several non-HLA genes were reported to be associated with susceptibility to T1D, including CTLA4, CD28, PTPN22, TCRβ, CD3z, IL15, BANK1, and ZAP70. In Arab countries, consanguinity, endogamy, and first-cousin marriage rates are some of the highest reported worldwide and are responsible for the creation of several inbreeding communities within the Arab world that have led to an increase in homozygosity of both the HLA haplotypes and non-HLA genes associated with either protection or susceptibility to T1D among Arabs. Homozygosity reduces the HLA complexity and is expected to facilitate our understanding of the mode of inheritance of HLA haplotypes and provide valuable insight into the intricate genotype-phenotype correlations in T1D patients. In this review, based on literature studies, I will discuss the current epidemiological profile and molecular genetic risks of Arabs with T1D.
1型糖尿病(T1D)是一种复杂的自身免疫性疾病,由T细胞介导的胰腺β细胞破坏引起,是环境因素与遗传因素相互作用的结果。尽管阿拉伯人是全球1型糖尿病发病率和患病率最高的群体之一,但遗憾的是,关于阿拉伯世界1型糖尿病的遗传流行病学信息匮乏。阿拉伯人与其他种族共享几种HLA单倍型,这些单倍型赋予对1型糖尿病的易感性或保护性,但他们也有与其他种族不同的特定单倍型。在不同的阿拉伯国家,有报道称几种非HLA基因与1型糖尿病易感性相关,包括CTLA4、CD28、PTPN22、TCRβ、CD3z、IL15、BANK1和ZAP70。在阿拉伯国家,近亲结婚、族内通婚和表亲结婚率是全球报道中最高的,这导致阿拉伯世界形成了几个近亲繁殖群体,使得与阿拉伯人对1型糖尿病的保护或易感性相关的HLA单倍型和非HLA基因的纯合性增加。纯合性降低了HLA复杂性,有望促进我们对HLA单倍型遗传模式的理解,并为1型糖尿病患者复杂的基因型-表型相关性提供有价值的见解。在这篇综述中,基于文献研究,我将讨论患有1型糖尿病的阿拉伯人的当前流行病学概况和分子遗传风险。