HLA associations

Last edited 11/2018

It is believed the HLA region on the short arm of chromosome 6 (ie, the IDDM1 locus) is responsible for one-half of the genetic susceptibility that leads to risk of type 1 diabetes (1)

• the strongest associations with T1D is seen in HLA class II type
• in Caucasians, particularly DR4-DQ8, are associated with a high risk of T1D, however, the exact HLA types may vary among different ethnic groups
• class I MHCs also seem to influence risk for type 1 diabetes, independent of class II molecules (1,2)

In addition certain DQ alleles which code for an amino acid other than aspartate at position 57 of the beta chain and/or arginine at position 52 of the alpha chain are significantly more common in the diabetic population. Interestingly DR2 is protective against IDDM. There are also associations with certain HLA class 1 antigens, for example B8 and B15.

Reference:

• (1) Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2013;383(9911):69-82
• (2) Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of diabetes in the young. Clin Diabetes Endocrinol. 2016;2:18.