A candidate gene study of risk for dementia in older, postmenopausal women: Results from the Women's Health Initiative Memory Study.
Aged
Alzheimer Disease
/ genetics
Apolipoproteins E
/ genetics
Brain-Derived Neurotrophic Factor
/ genetics
Catechol O-Methyltransferase
/ genetics
Cognitive Dysfunction
/ genetics
Dementia
/ genetics
Female
Genetic Predisposition to Disease
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
LDL-Receptor Related Proteins
/ genetics
Membrane Transport Proteins
/ genetics
Middle Aged
Mitochondrial Precursor Protein Import Complex Proteins
Polymorphism, Single Nucleotide
Postmenopause
Women's Health
AD
Alzheimer's disease
MCI
aging
hormone therapy
Journal
International journal of geriatric psychiatry
ISSN: 1099-1166
Titre abrégé: Int J Geriatr Psychiatry
Pays: England
ID NLM: 8710629
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
10
01
2018
accepted:
18
08
2018
pubmed:
2
2
2019
medline:
21
12
2019
entrez:
2
2
2019
Statut:
ppublish
Résumé
While a number of single nucleotide polymorphisms (SNPs) associated with Alzheimer's disease (AD) or cognitive impairment have been identified, independent replications remain the only way to validate proposed signals. We investigated SNPs in candidate genes associated with either cognitive impairment or AD pathogenesis and their relationships with probable dementia (PD) in the Women's Health Initiative Memory Study (WHIMS). We analyzed 96 SNPs across five genes (APOE/TOMM40, BDNF, COMT, SORL1, and KIBRA) in 2857 women (ages ≥65) from the WHIMS randomized trials of hormone therapy using a custom Illumina GoldenGate assay; 19% of the sample were MCI (N = 165) or PD (N = 387), and the remaining 81% were free of cognitive impairment. SNP associations were evaluated for PD in non-Hispanic whites adjusting for age and HT using logistic regression under an additive genetic model. One SNP (rs157582), located in the TOMM40 gene nearby APOE, was associated with the PD phenotype based on a P value accounting for multiple comparisons. An additional 12 SNPs were associated with the PD phenotype at P ≤ 0.05 (APOE: rs405509, rs439401; TOMM40: rs8106922, and KIBRA: rs4320284, rs11740112, rs10040267, rs13171394, rs6555802, rs2241368, rs244904, rs6555805, and rs10475878). Results of the sensitivity analyes excluding MCI were similar, with addition of COMT rs737865 and BDNF rs1491850 (P ≤ 0.05). Our results in older women provide supporting evidence that the APOE/TOMM40 genes confer dementia risk and extend these findings to COMT, BDNF, and KIBRA. Our findings may lead to a better understanding of the role these genes play in cognition and cognitive impairment.
Identifiants
pubmed: 30706571
doi: 10.1002/gps.5068
pmc: PMC6608707
mid: NIHMS1009206
doi:
Substances chimiques
Apolipoproteins E
0
Brain-Derived Neurotrophic Factor
0
Intracellular Signaling Peptides and Proteins
0
LDL-Receptor Related Proteins
0
Membrane Transport Proteins
0
Mitochondrial Precursor Protein Import Complex Proteins
0
SORL1 protein, human
0
TOMM40 protein, human
0
WWC1 protein, human
0
COMT protein, human
EC 2.1.1.6
Catechol O-Methyltransferase
EC 2.1.1.6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
692-699Subventions
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NIA NIH HHS
ID : R00 AG032361
Pays : United States
Organisme : National Institute on Aging, NIH
ID : K99AG032361
Pays : International
Organisme : National Heart, Lung and Blood Institute (NHLBI)
ID : HHSN-268-2004-6-4221C
Pays : International
Organisme : National Heart, Lung and Blood Institute (NHLBI)
ID : NIA: HHSN-271-2011-00004C; K99AG032361
Pays : International
Organisme : National Institute of Aging (NIA)
ID : HHSN-271-2011-00004C
Pays : International
Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
Alzheimer's Association. 2017 Alzheimer's disease facts and figures. Alzheimers Dement. 2017;13:325-373.
Heron M. Deaths: Leading causes for 2014. In: National Vital Statistics Reports. Vol.65 Hyattsville, MD: National Center for Health Statistics; 2016 5.
Glatt CE, Freimer NB. Association analysis of candidate genes for neuropsychiatric disease: the perpetual campaign. Trends Genet. 2002;18(6):307-312.
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921-923.
Kehoe P, Wavrant-De Vrieze F, Crook R, et al. A full genome scan for late onset Alzheimer's disease. Hum Mol Genet. 1999;8(2):237-245.
Cedazo-Minguez A, Cowburn RF. Apolipoprotein E: a major piece in the Alzheimer's disease puzzle. J Cell Mol Med. 2001;5(3):254-266.
O'Donoghue MC, Murphy SE, Zamboni G, Nobre AC, Mackay CE. APOE genotype and cognition in healthy individuals at risk of Alzheimer's disease: a review. Cortex. 2018;104:103-123.
Roses AD, Lutz MW, Amrine-Madsen H, et al. A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease. Pharmacogenomics J. 2010;10(5):3753-3784.
Davies G, Armstrong N, Bis JC, et al. Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949). Mol Psychiatry. 2015;20(2):183-192.
Andersen OM, Reiche J, Schmidt V, et al. Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc Natl Acad Sci U S A. 2005;102(38):13461-13466.
Annaert W, De Strooper B. A cell biological perspective on Alzheimer's disease. Annu Rev Cell Dev Biol. 2002;18(1):25-51.
Reitz C, Mayeux R. Use of genetic variation as biomarkers for Alzheimer's disease. Ann N Y Acad Sci. 2009;1180(1):75-96.
Rogaeva E, Meng Y, Lee JH, et al. The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease. Nat Genet. 2007;39(2):168-177.
Egan MF, Goldberg TE, Kolachana BS, et al. Effect of COMT Val108/158 met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A. 2001;98(12):6917-6922.
Serretti A, Olgiati P. Catechol-o-methyltransferase and Alzheimer's disease: a review of biological and genetic findings. CNS Neurol Disord Drug Targets. 2012;11(3):299-305.
Flirski M, Sobow T, Kloszewska I. Behavioural genetics of Alzheimer's disease: a comprehensive review. Arch Med Sci. 2011;7(2):195-210.
Perkovic MN, Strac DS, Tudor L, Konjevod M, Erjavec GN, Pivac N. Catechol-O-methyltransferase, cognition and Alzheimer's disease. Curr Alzheimer Res. 2018;15(5):408-419.
Baquet ZC, Gorski JA, Jones KR. Early striatal dendrite deficits followed by neuron loss with advanced age in the absence of anterograde cortical brain-derived neurotrophic factor. J Neurosci. 2004;24(17):4250-4258.
Figurov A, Pozzo-Miller LD, Olafsson P, Wang T, Lu B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature. 1996;381(6584):706-709.
Gorski JA, Zeiler SR, Tamowski S, Jones KR. Brain-derived neurotrophic factor is required for the maintenance of cortical dendrites. J Neurosci. 2003;23(17):6856-6865.
Lee JL, Everitt BJ, Thomas KL. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science. 2004;304(5672):839-843.
Fukumoto N, Fujii T, Combarros O, et al. Sexually dimorphic effect of the Val66Met polymorphism of BDNF on susceptibility to Alzheimer's disease: new data and meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2010;153B(1):235-242.
Papassotiropoulos A, Stephan DA, Huentelman MJ, et al. Common Kibra alleles are associated with human memory performance. Science. 2006;314(5798):475-478.
Almeida OP, Schwab SG, Lautenschlager NT, et al. KIBRA genetic polymorphism influences episodic memory in later life, but does not increase the risk of mild cognitive impairment. J Cell Mol Med. 2008;12(5A):1672-1676.
Burgess JD, Pedraza O, Graff-Radford NR, et al. Association of common KIBRA variants with episodic memory and AD risk. Neurobiol Aging. 2011;32(3):557.
Shumaker SA, Reboussin BA, Espeland MA, et al. The Women's Health Initiative memory study (WHIMS): a trial of the effect of estrogen therapy in preventing and slowing the progression of dementia. Control Clin Trials. 1998;19(6):604-621.
Coker LH, Espeland MA, Rapp SR, et al. Postmenopausal hormone therapy and cognitive outcomes: the Women's Health Initiative memory study (WHIMS). J Steroid Biochem Mol Biol. 2010;118(4-5):304-310.
Teng EL, Chui HC. The Modified Mini-Mental State (3MS) examination. J Clin Psychiatry. 1987;48(8):314-318.
American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders: DSM-IV [Internet]. 4th ed. Washington (DC): American Psychiatric Association; 1994 [cited 2010 Mar 8:866.
Cacciottolo M, Wang X, Driscoll I, et al. Particulate air pollutants, APOE alleles and their contributions to cognitive impairment in older women and to amyloidogenesis in experimental models. Transl Psychiatry. 2017;7(1):e1022.
Goveas JS, Rapp SR, Hogan PE, et al. Predictors of optimal cognitive aging in 80+ women: the Women's Health Initiative memory study. J Gerontol A Biol Sci Med Sci. 2016;71(Suppl 1):S62-S71.
Mozhui K, Snively BM, Rapp SR, Wallace RB, Williams RW, Johnson KC. Genetic analysis of mitochondrial ribosomal proteins and cognitive aging in postmenopausal women. Front Genet. 2017;8:127.
Jun G, Vardarajan BN, Buros J, et al. Comprehensive search for Alzheimer disease susceptibility loci in the APOE region. Arch Neurol. 2012;69(10):1270-1279.
Beecham GW, Hamilton K, Naj AC, et al. Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias. PLoS Genet. 2014;10(9):e1004606.
Chouraki V, Seshadri S. Genetics of Alzheimer's disease. Adv Genet. 2014;87:245-294.
Jin C, Liu X, Zhang F, et al. An updated meta-analysis of the association between SORL1 variants and the risk for sporadic Alzheimer's disease. J Alzheimers Dis. 2013;37(2):429-437.
Karch CM, Goate AM. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry. 2015;77(1):43-51.
Lin WY, Wu BT, Lee CC, et al. Association analysis of dopaminergic gene variants (Comt, Drd4 and Dat1) with Alzheimer s disease. J Biol Regul Homeost Agents. 2012;26(3):401-410.
Pereira PA, Romano-Silva MA, Bicalho MA, et al. Catechol-O-methyltransferase genetic variant associated with the risk of Alzheimer's disease in a Brazilian population. Dement Geriatr Cogn Disord. 2012;34(2):90-95.
Lanni C, Garbin G, Lisa A, et al. Influence of COMT Val158Met polymorphism on Alzheimer's disease and mild cognitive impairment in Italian patients. J Alzheimers Dis. 2012;32(4):919-926.
Dixon RA, DeCarlo CA, MacDonald SW, Vergote D, Jhamandas J, Westaway D. APOE and COMT polymorphisms are complementary biomarkers of status, stability, and transitions in normal aging and early mild cognitive impairment. Front Aging Neurosci. 2014;6:236.
Corneveaux JJ, Liang WS, Reiman EM, et al. Evidence for an association between KIBRA and late-onset Alzheimer's disease. Neurobiol Aging. 2010;31(6):901-909.
Rodriguez-Rodriguez E, Infante J, Llorca J, et al. Age-dependent association of KIBRA genetic variation and Alzheimer's disease risk. Neurobiol Aging. 2009;30(2):322-324.