title: Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group.
abstract: Decline in cognitive abilities is a major concern in aging individuals. A potential important factor for functioning of the central nervous system in late-life stages is the KLOTHO (KL) gene. KL is expressed in various organs including the brain and is involved in multiple biological processes, for example, growth factor signaling. In the present study, 19 tagging gene variants in KL were studied in relation to 2 measures of cognitive function, a 5-item cognitive composite score and the Mini Mental State Examination, in 1,480 Danes 92-100 years of age. We found that heterozygotes for the previously reported KL-VS had poorer cognitive function than noncarriers. Two other variants positioned in the 5' end of the gene, rs398655 and rs562020, were associated with better cognitive function independently of KL-VS, and the common haplotype AG was associated with poorer cognition, consistently across two cognitive measures in two cohort strata. The haplotype effect was stronger than that of KL-VS. Two variants, rs2283368 and rs9526984, were the only variants significantly associated with cognitive decline over 7 years. We discuss an age-dependent effect of KL and the possibility that multiple gene variants in KL are important for cognitive function among the oldest old participants.
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. jmengel-from@health.sdu.dk.
authors.forename: Jonas
authors.initials: J
authors.lastname: Mengel-From
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Soerensen
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nygaard
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Psychology, University of Minnesota, Minneapolis.
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000046:Academic Medical Centers; D000369:Aged, 80 and over; D000375:Aging; D000483:Alleles; D015415:Biomarkers / Q000378:metabolism; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics*; D003718:Denmark; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D015577:Geriatric Assessment; D005966:Glucuronidase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D011110:Polymorphism, Genetic; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Cognition; Cognitive; Dementia; KLOTHO; Longevity