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Abstract
The relationship between the geographic distribution of susceptibility genes to insulin
autoimmune syndrome (IAS) and the incidence of insulin autoimmune syndrome was investigated
in order to examine the distribution of the genetic background to susceptibility to
certain diseases. The HLA-DR4 allele, DRB1*0406, is associated with increased susceptibility
to IAS among Japanese, while the DRB1*0403 and DRB1*0407 alleles are not (the odds
ratio of which are 1.6 and 1.1, respectively). The worldwide geographic distribution
of the three DR*04 alleles showed that the distribution of DRB1*0403 encompassed that
of DRB1*0406 and DRB1*0407. Taken together with the findings that Glu at position
74 in the DRB1 molecule is shared by the three DRB1*04 alleles, there are only a few
differences between the DRB1 molecule-nucleotide sequences of DRB1*0403, DRB1*0406
and DRB1*0407, and that all the three DRB1*04 alleles are carried by the same class
II haplotype, DQA1*0301/DQB1*0302, it may be considered that DRB1*0403 is the ancestral
allele of DRB1*0406 and DRB1*0407. Therefore, populations with a higher prevalence
of DRB1*0406 have a higher risk of developing IAS. The extremely low prevalence of
IAS among Caucasians can be explained by the low prevalence of DRB1*0406 in this population.
This is a good example of the association between the predisposition to risk of development
of certain diseases and the evolution of susceptibility genes.