IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type

Sato, Noriko; Ueki, Akinori; Ueno, Hideo; Shinjo, Hidetaka; Morita, Yoshio

doi:10.1155/2008/858759

Cited by 4 publications

(4 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In earlier studies, no significant differences were detected for rs1999764 between patients with LOAD and controls in the allele and genotype frequencies, nor were there any associations when data were stratified by APOE∊4 status. 19 –21 In contrast, in the present study, an examination of the genotype and allele distribution showed that this SNP is highly linked to LOAD susceptibility, particularly in APOE∊4 noncarriers and female patients (Tables 3 and 4). Thus, further studies on different populations are warranted to identify any possible factors, including ethnic variability, which can account for the discrepancy in these findings.…”

Section: Discussioncontrasting

confidence: 85%

Association Between Polymorphisms of the Insulin-Degrading Enzyme Gene and Late-Onset Alzheimer Disease

Wang

2014

J Geriatr Psychiatry Neurol

View full text Add to dashboard Cite

The insulin-degrading enzyme (IDE) gene is a strong positional and biological candidate for late-onset Alzheimer disease (LOAD) susceptibility, with recent studies independently demonstrating an association between IDE gene variants and LOAD. However, previous data have been controversial. To investigate the relationship between IDE gene polymorphisms and LOAD risk, a case-control association study of 406 Han Chinese participants in Xinjiang, China, was undertaken. The LOAD and control groups consisted of 202 and 204 participants, respectively. The single-nucleotide polymorphisms rs1887922 and rs1999764 of the IDE gene were linked to LOAD incidence. The presence of the CT+CC genotype of rs1999764 had a protective effect compared to the TT genotype (adjusted P=.0001; odds ratio [OR]=0.226; 95% confidence interval [CI]=0.116-0.441), while the CT+CC genotype of rs1887922 was associated with increased LOAD risk (adjusted P=.0001; OR=3.640; 95% CI=1.889-7.016). Moreover, the effects of rs1887922 and rs1999764 were associated with LOAD risk independent of the apolipoprotein E ∊4 polymorphism and were more significant in men and women, respectively. These results demonstrate that the polymorphisms rs1887922 and rs1999764 of the IDE gene are associated with LOAD susceptibility in the Xinjiang Han population.

show abstract

Section: Discussioncontrasting

confidence: 85%

Association Between Polymorphisms of the Insulin-Degrading Enzyme Gene and Late-Onset Alzheimer Disease

Wang

2014

J Geriatr Psychiatry Neurol

View full text Add to dashboard Cite

show abstract

“…Indeed, IDE/HHEX genes have been linked to type 2 diabetes and elevated blood glucose level [ 12 , 13 ]. Although genetic association studies on SNPs in the IDE/HHEX region and AD have produced both positive and negative findings [ 14 ], several studies have suggested that genetic variations within the IDE/HHEX gene region may impact both diseases, and thus underlie the association between diabetes and AD [ 7 ]. So far, no studies have examined the role of IDE/HHEX genes in such an association in humans.…”

Section: Introductionmentioning

confidence: 99%

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

Pedersen

Keller

et al. 2015

PLoS Med

View full text Add to dashboard Cite

BackgroundResearch has suggested that variations within the IDE/HHEX gene region may underlie the association of type 2 diabetes with Alzheimer disease (AD). We sought to explore whether IDE genes play a role in the association of diabetes with dementia, AD, and structural brain changes using data from two community-based cohorts of older adults and a subsample with structural MRI.Methods and FindingsThe first cohort, which included dementia-free adults aged ≥75 y (n = 970) at baseline, was followed for 9 y to detect incident dementia (n = 358) and AD (n = 271) cases. The second cohort (for replication), which included 2,060 dementia-free participants aged ≥60 y at baseline, was followed for 6 y to identify incident dementia (n = 166) and AD (n = 121) cases. A subsample (n = 338) of dementia-free participants from the second cohort underwent MRI. HHEX_23 and IDE_9 were genotyped, and diabetes (here including type 2 diabetes and prediabetes) was assessed. In the first cohort, diabetes led to an adjusted hazard ratio (HR) of 1.73 (95% CI 1.19–2.32) and 1.66 (95% CI 1.06–2.40) for dementia and AD, respectively, among all participants. Compared to people carrying the GG genotype without diabetes, AA genotype carriers with diabetes had an adjusted HR of 5.54 (95% CI 2.40–7.18) and 4.81 (95% CI 1.88–8.50) for dementia and AD, respectively. There was a significant interaction between HHEX_23-AA and diabetes on dementia (HR 4.79, 95% CI 1.63–8.90, p = 0.013) and AD (HR 3.55, 95% CI 1.45–9.91, p = 0.025) compared to the GG genotype without diabetes. In the second cohort, the HRs were 1.68 (95% CI 1.04–2.99) and 1.64 (1.02–2.33) for the diabetes–AD and dementia–AD associations, respectively, and 4.06 (95% CI 1.06–7.58, p = 0.039) and 3.29 (95% CI 1.02–8.33, p = 0.044) for the interactions, respectively. MRI data showed that HHEX_23-AA carriers with diabetes had significant structural brain changes compared to HHEX_23-GG carriers without diabetes. No joint effects of IDE_9 and diabetes on dementia were shown. As a limitation, the sample sizes were small for certain subgroups.ConclusionsA variant in the HHEX_23 gene interacts with diabetes to be associated with a substantially increased risk of dementia and AD, and with structural brain changes among dementia-free elderly people.

show abstract

“…Go et al observed an association between NRG1 SNP, both in isolation and as part of a 3-loci haplotype, and a psychotic phenotype in AD [ 111 ]. Another effort to dissect the genetic background of BPSD focused on the IDE gene coding for insulin-degrading enzyme protein [ 112 ]. The IDE plays a key role in degrading several important peptides, including Aα.…”

Section: Other Genesmentioning

confidence: 99%

“…The IDE plays a key role in degrading several important peptides, including Aα. A correlation was observed between carrying the C allele of the IDE gene and the risk for affective disturbances in AD, with no effect on other behavioural symptoms [ 112 ].…”

Section: Other Genesmentioning

confidence: 99%

Behavioural genetics of Alzheimer's disease: a comprehensive review

Flirski¹,

Sobów²,

Kłoszewska³

2011

aoms

View full text Add to dashboard Cite

Behavioural and psychological symptoms of dementia (BPSD) are present in the course of the illness in up to 90% of patients with Alzheimer's disease (AD). They are the main source of caregiver burden and one of the major factors contributing to early institutionalization. The involvement of a genetic component in BPSD aetiology seems beyond controversy, though the exact significance of particular polymorphisms is uncertain in the majority of cases. Multiple genes have been assessed for their putative influence on BPSD risk. In this paper we review the behavioural genetics of AD, particularly the importance, with respect to BPSD risk, of genes coding for apolipoprotein E and proteins involved in the process of neurotransmission: serotonin receptors, serotonin transporter, COMT, MAO-A, tryptophan hydroxylase and dopamine receptors. A general conclusion is the striking inconsistency of the findings, unsurprising in the field of psychiatric genetics. The potential reasons for such discrepancy are exhaustively discussed.

show abstract

IDE Gene Polymorphism Influences on BPSD in Mild Dementia of Alzheimer's Type

Cited by 4 publications

References 36 publications

Association Between Polymorphisms of the Insulin-Degrading Enzyme Gene and Late-Onset Alzheimer Disease

Association Between Polymorphisms of the Insulin-Degrading Enzyme Gene and Late-Onset Alzheimer Disease

HHEX_23 AA Genotype Exacerbates Effect of Diabetes on Dementia and Alzheimer Disease: A Population-Based Longitudinal Study

Behavioural genetics of Alzheimer's disease: a comprehensive review

Contact Info

Product

Resources

About