title: Impact of genetic variations in the WRN gene on age related pathologies and mortality.
abstract: Mutations in the WRN gene lead to the Werner syndrome (WS), which resembles premature aging. Here, we hypothesize that genetic variations in the WRN gene may also influence aging-trajectories in the population at large. To test this hypothesis, we assessed the impact of the i1-C/T, L1074F and C1367R polymorphisms in the WRN gene on the occurrence of cardiovascular pathologies, on cognitive performance and on the risks of all-cause, cardiovascular and cancer mortalities in the population-based Leiden 85-plus Study. This prospective follow-up study includes 1,245 participants aged 85 years and older, with a total follow-up of 5,164 person-years. At baseline the risks of myocardial infarction, myocardial ischemia, intermittent claudication, arterial surgery and stroke dependent on the i1-C/T, L1074F and C1367R polymorphisms, did not vary between the different genotypes. Also no differences in cognitive functioning were observed, except for attention, where carriers of the 1367R allele performed worse compared to the 1367C homozygotes (94.2 (4.35) versus 84.8 (1.84), p=0.04). Mortality risks, calculated separately for all SNPs, were similar between the different genotype carriers of the i1-C/T, L1074F and C1367R polymorphisms, showing no evidence of altered survival. In conclusion, the i1-C/T, L1074F and C1367R polymorphisms in the WRN gene do not influence the aging-trajectories and survival in the population at large.
authors.affiliation: Department of Gerontology and Geriatrics C2-R, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Maris
authors.initials: M
authors.lastname: Kuningas
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology*; D019943:Amino Acid Substitution; D003072:Cognition Disorders / Q000235:genetics / Q000401:mortality / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics*; D005090:Exodeoxyribonucleases; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007383:Intermittent Claudication / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000401:mortality / Q000473:pathology; D009369:Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D053484:RecQ Helicases; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase