Authors: Castro E; Ogburn CE; Hunt KE; Tilvis R; Louhija J; Penttinen R; Erkkola R; Panduro A; Riestra R; Piussan C; Deeb SS; Wang L; Edland SD; Martin GM; Oshima J
Abstract: 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.
Keywords: Adult; Aged; Aged, 80 and over; Aging; Apolipoproteins E/genetics; Blood/metabolism; Fetal Blood/metabolism; Finland; Gene Frequency; Genotype; Humans; Infant, Newborn; Middle Aged; Models, Genetic; Mutation, Missense; *Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Werner Syndrome/ethnology/*genetics|
Journal: American journal of medical genetics Volume: 82 Issue: 5 Pages: 399-403 Date: March 9, 1999 PMID: 10069711 |
The 1367 Cys/Arg polymorphism was examined during aging in 175 Finnish centenarians and 178 newborns, 169 Mexican newborns, 23 North American adults and 198 Japanese adults.
When newborns and centenarians were compared within the Finnish population no differences were observed in the proportions of 1367 Cys/Arg across age groups. 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.
Castro E, Ogburn CE, Hunt KE, Tilvis R, Louhija J, Penttinen R, Erkkola R, Panduro A, Riestra R, Piussan C, Deeb SS, Wang L, Edland SD, Martin GM, Oshima J (1999) Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians. American journal of medical genetics 82: 399-403.
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