genetic factors

Last edited 12/2018

Type 1 diabetes has been clearly shown to be a polygenic disorder, with nearly 40 loci known to affect disease susceptibility (1)

Risk of developing the disease is higher in relatives of diabetic patients. In siblings, the risk is greater than in offsprings, and there is a high concordance rate among identical twins (2)

The HLA region of chromosome 6 is most closely linked to susceptibility to IDDM:

• the inheritance of particular HLA alleles can account for over half of the genetic risk of developing type 1 diabetes (3)
  • genes encoding class II MHC proteins are most strongly linked with diabetes, and these genes are called HLA-DR, HLA-DQ, and HLA-DP
  • in the general population, only half of the people inherit a copy (allele) of DR gene called DR3 and DR4, and less than 3% of the people have two alleles
    • however, in type 1 diabetes at least one allele of DR3 or DR4 is found in 95% of Caucasians, and individuals with both DR3 and DR4 are particularly susceptible to type 1 diabetes (4)
    • conversely, the DR2 allele is protective for development of IDDM (5)

Other genes such as the insulin gene on chromosome 11 have been implicated.

Reference:

• (1) Unnikrishnan R, Shah VN, Mohan V. Challenges in diagnosis and management of diabetes in the young. Clin Diabetes Endocrinol. 2016;2:18.
• (2) Precechtelova J et al.Type I diabetes mellitus: genetic factors and presumptive enteroviral etiology or protection. J Pathog. 2014;2014:738512
• (3) Todd J A , Bell J I , McDevitt H O . et al. HLA-DQ beta gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature. 1987;329:599-604
• (4) Wolf E , Spencer K M , Cudworth A G . et al. The genetic susceptibility to type 1 (insulin-dependent) diabetes: analysis of the HLA-DR association. Diabetologia. 1983;24:224-230
• (5) Platz P , Jakobsen B K , Morling N . et al. HLA-D and -DR antigens in genetic analysis of insulin dependent diabetes mellitus. Diabetologia. 1981;21:108-115.