Juxtaposition of Coeliac Disease and Type 1 Diabetes; the Role of Shared Nonhuman Leukocyte Antigen Loci

Although extensive studies have been performed to explore the role of various alleles within the human leukocyte antigen (HLA) in susceptibility to coeliac disease (CD) and type 1 diabetes (T1D), less attention has been dedicated to the role of shred nonHLA loci. In the present report, we have provided a review on the role of genetic variants in seven shared nonHLA loci in determining the risk of either CD or T1D. The literature search was done on the Web of Knowledge, PubMed, and Scopus databases using keywords of polymorphism, coeliac disease, and type 1 diabetes. The literature published within 20002017 were recruited. Seven discussed shared loci between CD and T1D were those resided within cytotoxic Tlymphocyte associated protein 4 (CTL4), regulator of G protein signaling (RGS1), SH2B adaptor protein (SH2B3), T cell activation Rho GTPase activating protein (TAGAP), interleukin 18 receptor accessory protein (IL18RAP), protein tyrosine phosphatase, nonreceptor type (PTPN2), and CC motif chemokine receptor (CCR5). The interaction between polymorphisms of these genes seems to exert a substantial impact on determining the risk of CD and T1D in context of each other. Polymorphisms residing in these loci can exert synergistic or opposing effects toward either protection or predisposition to CD and T1D. The majority of these polymorphisms affect the function of cytokine signaling or T cell activating pathways. The net outcome deems to be delineated by a complex interaction between these adaptor arms, as well as the modulatory effects of other components of immune system, in particular, HLA alleles.