Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cy/Arg, and its stability in a population of Finnish centenarians

The Werner syndrome gene (WRN) encodes a novel helicase of 1,432 amino acid s. Homozygous mutations, all of which result in the truncation of the prote in, 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 polym orphism 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 hig her than those of 1367 Arg in all the populations examined, though the freq uencies varied among populations. The frequency of the 1367 Arg allele, tho ught to be protective against myocardial infarction in a Japanese populatio n, was approximately three times higher in the North American and Finnish a dult populations. When newborns and centenarians were compared within the F innish population, no differences were observed in the proportions of 1367 Cys/Arg across age groups, Within the Finnish population, we confirmed a si gnificant decrease of the APOE epsilon 2 allele and an increase in the epsi lon 4 allele in newborn infants compared with centenarians. Thus, unlike th e APOE polymorphism, there is no evidence of an association of this WRN pol ymorphism with longevity. (C) 1999 Wiley-Liss, Inc.