Genetic variation behind type 1 diabetes development
Tuesday September 12th, 2017
A specific genetic variation could lead to late onset type 1 diabetes, a European conference hears today.
Research being presented at the European Association for the Study of Diabetes (EASD) in Lisbon, Portugal, is the first to suggest that this could be the reason.
Dr Nick Thomas, Professor Andrew Hattersley and colleagues at the University of Exeter, England, looked at whether the increased risk of type 1 diabetes in children and young adults with the DR3 and DR4 genotypes continues into adulthood.
They analysed the development of type 1 diabetes in 120,000 individuals, aged from birth to 60 years, from the UK Biobank, selected from the highest risk HLA groups.
They found that although the highest risk genotypes made up just 6.4% of the UK population, they contributed 61% of all cases of type 1 diabetes and that within these high-risk groups, there were marked differences in both the likelihood of developing T1D and the average age of diagnosis.
In the high-risk HLA groups DR3/DR3, DR3/DR4 and DR4/DR4 there were marked differences in likelihood of developing T1D during a person's lifetime of 1.2%, 4.2%, and 3.5% respectively.
The authors found that for the DR3/DR3, DR3/DR4, and DR4/DR4 genotypes, the mean age of diagnosis was 17, 28, and 38 years old respectively, with 71% of T1D cases associated with the DR4/DR4 genotype being diagnosed in individuals over the age of 30. For DR3/DR3/ just 26% were diagnosed over 30, while for DR3/DR4 the figure was 40%.
They conclude: “Whilst all three major genotypes greatly increase risk of T1D throughout life, population analysis has shown for the first time that DR4/DR4 specifically predisposes to T1D over 30 years of age and carriers of this genotype have the highest risk for development of late-onset T1D.
“This is clear evidence that type 1 diabetes after 30 years is not just a delayed version of type 1 diabetes before 30. Further work is needed to understand these differences."
Abstract: 7 New insights into HLA in type 1 diabetes from population analysis: DR4 homozygosity specifically predisposes to type 1 diabetes after 30 years [abstract]
Printer friendly page