Behcet's disease (BD), also known as the Silk Road disease, is a blinding i
nflammatory disorder of young adults found predominantly between the Medite
rranean basin and the Orient, and is strongly associated with the major his
tocompatibility complex (MHC) antigen HLA-B51. In this article we review th
e history of Behcet's disease since its first description by Hippocrates, t
he development of the trading routes collectively known as the Silk Road an
d the effect of population movement on the distribution of HLA-B51. The glo
bal distribution of this antigen among healthy control populations bears a
striking similarity both to the ancient trading routes and the distribution
of Behcet's disease, suggesting a genetic risk that migrated in parallel w
ith population movement between the Mediterranean and Asia. However, certai
n indigenous Amerindian peoples have a high prevalence of HLA-B51 but no re
ported cases of ED. Furthermore, a clear genealogical relationship exists b
etween eastern, but not central, Siberian populations with the Amerindians,
Since a high level of recombination within the MHC is known to have occurr
ed in these eastern populations before their migration into Beringia, we su
ggest that disruption of genetic loci in linkage disequilibria with HLA-B51
may be one reason for the absence of disease in these high HLA-BS1-bearing
populations. However, a contributory influence of environmental factors is
not excluded by this data, and the wide variation that exists in relative
risk of HLA-B51 even within Europe would support other non-genetic risk fac
tors on the Silk Road which may be absent, or non-contributory to disease,
in the Americas.