Department of Pathology, University of Washington, Seattle 98195, USA.
Polymorphisms at the
Werner locus: I. Newly identified
polymorphisms, ethnic variability of 1367Cy/Arg, and its
stability in a population of Finnish centenarians.
American Journal of Medical Genetics. 82(5):399-403, 1999 Feb 19.
The Werner syndrome gene (WRN) encodes a
novel helicase of 1,432 amino acids. Homozygous mutations, all of which
result in the truncation of the protein,
lead to Werner syndrome. However, little is known about
the role of WRN in "normal" aging. We have identified four
missense polymorphisms and four conservative polymorphsims
in WRN gene. A single study showed that a polymorphism at amino acid 1367
Cys(TTG)/ Arg(CTG) is associated with a variation in risk of myocardial
infarction among a Japanese population. The 1367 Cys/Arg
polymorphism was examined during aging in three different populations:
Finnish, Mexican, and North American. The frequencies of
1367 Cys were higher than those of 1367 Arg in all the
populations examined, though the frequencies varied among
populations. The frequency of the 1367 Arg
allele, thought to be protective against myocardial infarction in a Japanese
population, was approximately three times higher in the
North American and Finnish adult populations. When newborns and centenarians
were compared within the Finnish population, no differences
were observed in the proportions of 1367 Cys/Arg across age
groups. Within the Finnish population, we confirmed a
significant decrease of the APOE epsilon2 allele and an
increase in the epsilon4 allele in newborn infants compared
with centenarians. Thus, unlike the APOE polymorphism,
there is no evidence of an association of this WRN
polymorphism with longevity.
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