Celiac Disease and Type 1 Diabetes in Families: A Systematic Review of Genetic Association

Abstract

Type 1 Diabetes (T1D) and Celiac Disease (CeD) often co-occur, indicating a shared genetic predisposition. This systematic review synthesizes current evidence on their genetic relationship, highlighting familial risk implications. A thorough search across databases including PubMed/MEDLINE and SCOPUS led to the inclusion of eleven studies that investigated the genetic link between these conditions. Notably, the Human Leukocyte Antigen (HLA) region, particularly the DQ2 and DQ8 haplotypes, emerged as the primary shared genetic risk factor. Additionally, specific HLA class II and I alleles were found to modulate the risks further associated with both diseases. Beyond HLA, non-HLA gene polymorphisms, such as those in PTPN22, INS, and MSH5, contribute to the shared susceptibility and distinguish between T1D alone and T1D with CeD. The review indicates an underlying immune dysregulation characterized by altered cytokine levels and suggests molecular mimicry as a potential mechanism due to homologous epitopes present in the auto-antigens of both conditions. The findings reflect a complex genetic architecture primarily centered on the HLA region, alongside relevant non-HLA immune-related genes, explaining the familial aggregation of T1D and CeD. While universal HLA screening for T1D may not be economically viable, targeted HLA genotyping, particularly when integrated with additional risk markers, is promising for identifying high-risk individuals for CeD, facilitating proactive monitoring, and stratifying familial risk.

Affiliated Institutions

• Maternity and Children's Hospital SA
• Shaqra University SA
• Primary Health Care QA
• Qassim University SA
• King Faisal University SA

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