Worldwide differences in the incidence of insulin autoimmune syndrome (Hirata disease) with respect to the evolution of HLA-DR4 alleles

The relationship between the geographic distribution of susceptibility gene s to insulin autoimmune syndrome (IAS) and the incidence of insulin autoimm une syndrome was investigated in order to examine che distribution of the g enetic background to susceptibility to certain diseases. The HLA-DR4 allele , DRB1*'0406, is associated with increased susceptibility to IAS among Japa nese, 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 encom passed that of DRB1*0406 and DRB1*0407. Taken together with the findings th at Glu at position 74 in the DRB1 molecule is shared by the three DRB1*04 a lleles, there are only a few differences between the DRB1 molecule-nucleoti de 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*0 406 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 Le explained by the low prevalence of DRB1*0406 in this population. This is a good example of the association between the pre disposition to risk of development of certain diseases and the evolution of susceptibility genes. Human Immunology 61, 154-157 (2000). (C) American So ciety for Histocompatibility and Immunogenetics, 2000. published by Elsevie r Science Inc.