IDDM

IDDM affects about 3 per 1000 of the population in the
UK and is a T cell dependent autoimmune disease. Genetic
predisposition is important, but only 30% of monozygous
twins are concordant for the disease and this indicates that
environmental factors (such as triggering viral infections)
are also involved. About 60% of the genetic susceptibility to
IDDM is likely to be due to genes in the HLA region. The
overall risk to siblings is about 6%. This figure rises to 16% for
HLA identical siblings and falls to 1% if they have no shared
haplotype. An association with DR3 and DR4 class II antigens is
well documented, with 95% of insulin dependent diabetics
having one or both antigens, compared to 50–60% of the
normal population. As most people with DR3 or DR4 class II
antigens do not develop diabetes, these antigens are unlikely
to be the primary susceptibility determinants. Better definition
of susceptible genotypes is becoming possible as subgroups of
DR3 and DR4 serotypes are defined by molecular analysis.
For example, low risk HLA haplotypes that confer protection
always have aspartic acid at position 57 of the DQB1 allele.
High risk haplotypes have a different amino acid at this
position and homozygosity for non-aspartic acid residues is
found much more often in diabetics than in non-diabetics.