title: KIBRA genetic polymorphism influences episodic memory in later life, but does not increase the risk of mild cognitive impairment.
abstract: A common T-->C polymorphism of the KIBRA gene has been recently associated with worse performance on tests of episodic memory. This should aimed to determine whether older adults with the KIBRA CC genotype (1) have worse episodic memory than T-allele carriers and, (2) are more likely to express the phenotype of amnestic mild cognitive impairment (MCI). Our Cross-sectional investigation of 312 adults aged 50-89 years free of dementia included genotyping of the KIBRA rs17070145 gene and the assessment of episodic memory to Establish a Registry for Alzheimer's Disease (CERAD). Participants were considered to have MCI if their memory scores were 1.5 standard deviations below the mean norm for the population. 138/312 participants carried the KIBRA CC genotype. Their immediate and delayed recall scores were significantly lower than the scores of carriers of the T allele (P < 0.05; adjusted for age, gender and pre-morbid IQ), although the effect size of the CC genotype was weak (0.2). Amongst our volunteers, 133 had MCI, of whom 63 (47.4%) had the CC genotype. There was no association between KIBRA genotype and MCI phenotype (TT/CT versus CC; adjusted odds ratio = 1.70, 95%CI = 0.74, 3.90). We concluded that the KIBRA T-->C polymorphism contributes to modulate episodic memory amongst community-dwelling older adults free of dementia, but plays no obvious role in the phenotypic expression of MCI. Future studies should aim to clarify the long term implications of this polymorphism on cognitive function and to identify other genes involved in the modulation of memory that might confer greater risk of MCI in later life.
authors.affiliation: WA Centre for Health & Ageing, Western Australian Institute for Medical Research, Australia. osvaldo.almeida@uwa.edu.au
authors.forename: O P
authors.initials: OP
authors.lastname: Almeida
authors.forename: S G
authors.initials: SG
authors.lastname: Schwab
authors.forename: N T
authors.initials: NT
authors.lastname: Lautenschlager
authors.forename: B
authors.initials: B
authors.lastname: Morar
authors.forename: K R
authors.initials: KR
authors.lastname: Greenop
authors.forename: L
authors.initials: L
authors.lastname: Flicker
authors.forename: D
authors.initials: D
authors.lastname: Wildenauer
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008568:Memory / Q000502:physiology*; D010750:Phosphoproteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D011506:Proteins; C513637:WWC1 protein, human