Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people

NEUROBIOLOGY OF AGING

卷:31

Article

Cluett, Christie¹  Brayne, Carol²  Clarke, Robert³  Evans, Grimley⁴  Matthews, Fiona⁵  Rubinsztein, David C.⁶  Huppert, Felicia⁷  Llewellyn, David J.²  Rice, Neil¹  Henley, William¹  Frayling, Timothy M.¹  Murray, Anna¹  Melzer, David¹ 

[1] Peninsula Med Sch, Exeter EX2 5DW, Devon, England

[2] Univ Forvie Site, Dept Publ Hlth & Primary Care, Cambridge CB2 0SR, England

[3] Univ Oxford, Clin Trial Serv Unit, Oxford OX3 7LF, England

[4] Univ Oxford Green Coll, Oxford OX2 6HE, England

[5] Inst Publ Hlth, MRC Biostat Unit, Cambridge CB2 0SR, England

[6] Addenbrookes Hosp, Cambridge Inst Med Res, Dept Med Genet, Cambridge CB2 2XY, England

[7] Addenbrookes Hosp, Acad Dept Psychiat, Cambridge CB2 2XY, England

关键词: Late-onset Alzheimer's disease;    Dementia;    Cognitive function;    Cognitive impairment;    Gene;    Single nucleotide polymorphism;    ApoE;    LMNA;   

DOI  :  10.1016/j.neurobiolaging.2008.08.020

来源: Elsevier

【 摘 要 】

A recent genome-wide association (GWA) study of late-onset Alzheimer's disease (LOAD) identified 15 novel single nucleotide polymorphisms (SNPs) independent of ApoE We hypothesised that variants associated with LOAD are also associated with poor cognitive function in elderly populations We measured additive associations between the five most strongly associated LOAD SNPs and grouped Mini Mental State Examination (MMSE) scores Variants were genotyped in respondents (mean age 79 years) from the Oxford Healthy Ageing project (OHAP) and other sites of the MRC Cognitive Function and Ageing Study (MRC-CFAS) In adjusted ordinal logistic models, two variants were associated with poorer cognitive function rs11622883 (OR=1.14, 95% CI 1 01-1 28, p=0 040) and rs505058 (OR=1.29. 95% CI 1 02-1 64, p=0 036). These SNPs are close to a SERPINA gene cluster and within LMNA, respectively The mechanisms underlying the associations with cognitive impairment and LOAD require further elucidation, but both genes are interesting candidates for involvement in age-related cognitive impairment (C) 2008 Elsevier Inc All rights reserved

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