Authors
  Carey MC.  Paigen B.
Title
  Epidemiology of the American Indians' burden and its likely genetic
  origins [Review]
Source
  Hepatology. 36(4 Part 1):781-791, 2002 Oct.
Abstract
It was not known until recently whether the endemic of cholesterol
gallstones among certain southwestern American Indian tribes was unique
among this ethnic group. With use of ultrasonography of the gallbladder and
standard diagnostic criteria, gallstones arc now found in epidemic
proportions in 13 diverse American Indian tribes and communities living in
Arizona, Oklahoma, and the Dakotas. We speculate that this redisposition is
polygenic involving "thrifty" genes that conferred survival advantages when
Paleo-Indians migrated from present-day Siberia to the Americas during the
last Great Ice Age approximately 50,000 to 10,000 years ago. A reasonable
hypothesis is that functioning of these genes promoted more efficient
caloric utilization and storage in the form of adipose tissue. Beneficial
results would have been operative during the isolation of Paleo-Indians in
the Bering Strait land bridge (Beringia) when thrifty genes would have
ensured sufficient fat reserves for survival of prolonged winters,
successful pregnancy outcomes, and extended lactation periods. The authors'
conjoint work on genetics of experimental cholesterol cholelithiasis in
inbred mice promises help in pinpointing orthologous genetic loci (LITH
genes) in the human genome. Moreover, the shared environments and
homogeneity of American Indian tribes and communities should facilitate
discovery of the ensembles of their common and rarer cholesterol gallstone
gcnes. It is anticipated that knowledge of expression, polymorphisms, and
functionality of LITH genes will help resolve the molecular mechanisms of
this complex heterogeneous trait and thereby provide targets for novel
therapies to prevent cholesterol cholelithiasis worldwide. [References: 70]
Institution
  Reprint available from:
  Carey MC
  Brigham & Womens Hosp, Div Gastroenterol, Ctr Digest Dis
  Thorn 1430,75 Francis St
  Boston, MA 02115
  USA





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