Type 1 diabetes

HLA-DR3-DQ2 / DR4-DQ8

In type 1 diabetes the immune system destroys the insulin-producing cells of the pancreas. The largest genetic contribution comes from the HLA region: the haplotypes DR3-DQ2 and DR4-DQ8 raise risk, their combination especially strongly, while other types protect.

Risk and protective haplotypes

DR3-DQ2 and DR4-DQ8 are the two most important risk haplotypes. Those who carry both have a clearly higher risk than carriers of only one. Conversely, DQB1*06:02 protects strongly. These opposing effects make the HLA locus the strongest single factor of type 1 diabetes risk.

Context

Even the highest HLA risk is not a prediction of disease. Most carriers of the risk haplotypes never develop type 1 diabetes. Islet cell autoantibodies and glucose metabolism become meaningful; Genome only provides the HLA context.

What Genome measures. Presence of the risk haplotypes DR3-DQ2 (DRB1*03:01-DQB1*02:01) and DR4-DQ8 (DRB1*04-DQB1*03:02) and of protective types such as DQB1*06:02 in the HLA typing.

Related topics

HLA and autoimmunityCeliac diseaseAutoimmune thyroid (Hashimoto, Graves)

Sources

  1. 1Noble & Erlich, 2012 Genetics of type 1 diabetes. Cold Spring Harbor Perspectives in Medicine 2:a007732. doi.org/10.1101/cshperspect.a007732
  2. 2Pociot & Lernmark, 2016 Genetic risk factors for type 1 diabetes. The Lancet 387:2331–2339. doi.org/10.1016/S0140-6736(16)30582-7