Which genes are associated with susceptibility to type 1 diabetes mellitus (DM)?

Updated: Oct 08, 2021
  • Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD  more...
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The insulin gene (INS), which encodes for the pre-proinsulin peptide, is adjacent to a variable number of tandem repeats (VNTR) polymorphism at chromosome 11p15.5. [28] Different VNTR alleles may promote either resistance or susceptibility to type 1 DM through their effect on INS transcription in the thymus; for example, protective VNTRs are associated with higher INS expression, which may promote deletion of insulin-specific T cells. [29]

Other genes that have been reported to be involved in the mechanism of type 1 DM include CTLA4 (important in T-cell activation), PTPN22 (produces LYP, a negative regulator of T-cell kinase signaling), and IL2RA (encodes for CD25 which is involved with regulating T-cell function). UBASH3A (also known as STS2), may be involved in the increased risk not only of type 1 DM but also of other autoimmune disease and Down syndrome; it is located on locus chromosome 21q22.3. [30]

In addition, genome-wide association studies have implicated numerous other genes, including the following [31] :

  • SH2B3

  • ERBB3

  • CLEC16A

  • IL18RAP

  • PTPN2

  • CCR5

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