Juxtaposition of Coeliac Disease and Type 1 Diabetes; the Role of Shared Non-Human Leukocyte Antigen Loci

Iraj Shahramian,Nosratollah Masinaeinejad,Mojtaba Delaramnasab,Hossein Shahdadi,Ali Bazi

doi:10.15171/ijbsm.2018.01

Iraj Shahramian, Nosratollah Masinaeinejad + Show 3 more

Open Access

https://doi.org/10.15171/ijbsm.2018.01

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Abstract

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 non-HLA loci. In present report, we have provided a review on the role of genetic variants in seven shared non-HLA loci in determination 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 2000-2017 were recruited. Seven discussed shared loci between CD and T1D were those resided within cytotoxic T-lymphocyte 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, non-receptor type (PTPN2), and C-C motif chemokine receptor (CCR5). Interaction between polymorphisms of these genes seems to exert a substantial impact on determination 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.

Highlights

Coeliac disease (CD), an autoimmune disorder inflicting gastrointestinal system, is a common enteropathy characterized with intestinal inflammation.[1]
Abstract 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 non-HLA loci
We have provided a review on the role of genetic variants in seven shared non-HLA loci in determining the risk of either CD or T1D

Summary

Introduction

Coeliac disease (CD), an autoimmune disorder inflicting gastrointestinal system, is a common enteropathy characterized with intestinal inflammation.[1]. Inheritance of rs231775 ( +49 A/G) polymorphism was shown to be linked to dampen levels of CLTA4 in both plasma and cell surface of T lymphocytes.[45] These reduced levels, which subsequently lead to lower immunomodulatory effects of CTLA-4, have been accompanied with a higher rate of autoimmune conditions such as T1D, Graves disease, and graft rejection in transplanted individuals.[46,47] Multiple studies have noted predisposing role for minor G allele of this polymorphism for CD18 and T1D.13-15,19-24. Individuals with homozygote signature for A allele may develop autoimmune conditions indicating a multidisciplinary interaction for detraining risk of autoimmunity.[45] immune reactions are dependent on a complex interaction of non-HLA loci mediators with those of HLA II alleles This is substantially important as HLA II molecules impart a significant role in antigen presentation to reactive T lymphocytes.

Celiac Disease

Findings

Conclusion