Case-control study and meta-analysis of low density lipoprotein receptor-related protein gene exon 3 polymorphism in Alzheimer's disease

Sánchez-Guerra, Marisa; Combarros, Onofre; Infante, Jon; Llorca, Javier; Berciano, José; Fontalba, Ana; Fernández-Luna, José L.; Peña, Nicolás; Fernández-Viadero, Carlos

doi:10.1016/s0304-3940(01)02342-4

Cited by 45 publications

(36 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[20][21][22]44 Herein we found that the þ 766C4T polymorphism of exon 3 of the LRP gene was not associated, when analysed alone, with an increased risk of AD (OR 1.2 (95% CI, 0.9-1.8), P ¼ 0.24) although a metaanalysis of all previous works indicated a modest association between the CC genotype and AD (OR 1.35 (95% CI, 1.1-1.7), P ¼ 0.01). 45 We also found a trend for association between the A to G substitution of MAPK8IP1 and an increased risk of AD when the two studies were pooled together, and the association in early-onset AD should be only a chance result. The IB1/JIP-1 polymorphism becomes a significant risk of AD in subjects bearing the CC genotype in exon 3 of the LRP gene (OR 2.1 (95% CI, 1.2-3.7), P ¼ 0.01), suggesting a possible additive effect of these two gene variants in the risk of AD.…”

Section: Discussionmentioning

confidence: 52%

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

View full text Add to dashboard Cite

Islet-brain1 (IB1) or c-Jun NH2 terminal kinase interacting protein-1 (JIP-1), the product of the MAPK8IP1 gene, functions as a neuronal scaffold protein to allow signalling specificity. IB1/ JIP-1 interacts with many cellular components including the reelin receptor ApoER2, the lowdensity lipoprotein receptor-related protein (LRP), kinesin and the Alzheimer's amyloid precursor protein. Coexpression of IB1/JIP-1 with other components of the c-Jun NH2 terminal-kinase (JNK) pathway activates the JNK activity; conversely, selective disruption of IB1/JIP-1 in mice reduces the stress-induced apoptosis of neuronal cells. We therefore hypothesized that IB1/JIP-1 is a risk factor for Alzheimer's disease (AD). By immunocytochemistry, we first colocalized the presence of IB1/JIP-1 with JNK and phosphorylated tau in neurofibrillary tangles. We next identified a À499A4G polymorphism in the 5' regulatory region of the MAPK8IP1 gene. In two separate French populations the À499A4G polymorphism of MAPK8IP1 was not associated with an increased risk to AD. However, when stratified on the þ 766C4T polymorphism of exon 3 of the LRP gene, the IB1/JIP-1 polymorphism was strongly associated with AD in subjects bearing the CC genotype in the LRP gene. The functional consequences of the -499A4G polymorphism of MAPK8IP1 was investigated in vitro. In neuronal cells, the G allele increased transcriptional activity and was associated with an enhanced binding activity. Taken together, these data indicate that the increased transcriptional activity in the presence of the G allele of MAPK8IP1 is a risk factor to the onset of in patients bearing the CC genotype of the LRP gene.

show abstract

Section: Discussionmentioning

confidence: 52%

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Sánchez-Guerra et al (2001) conducted a meta-analysis of eight studies and found a weak correlation between the LRP CC genotype and AD. Pritchard et al (2005) performed a meta-analysis on the data of 4668 patients with AD and 4473 control subjects but found no evidence for the involvement of the LRP C/T polymorphism in either increasing the susceptibility to AD, or acting as a phenotypic modifier.…”

Section: Discussionmentioning

confidence: 99%

“…Low-density lipoprotein receptor-related protein (LRP) is a cell receptor for APOE and is involved in mediating APOE-dependent neurite growth and in the neuronal metabolism of secreted β-amyloid precursor proteins (Kounnas et al, 1995;Sánchez-Guerra et al, 2001). Kang et al (1997) were the first to report that a polymorphism in exon 3 of LRP is a risk factor for AD.…”

Section: Introductionmentioning

confidence: 99%

Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer’s disease in the Chinese population: a meta-analysis of case-control studies

Yang

Zhou

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The objective of this study was to assess the associations of presenilin 1 (PS1) 1/2, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D), and low-density lipoprotein receptor-related protein (LRP) C/T polymorphisms with the risk of Alzheimer's disease (AD) in the Chinese population. PS1 1/2, ACE I/D, and LRP C/T, which are commonly investigated polymorphisms, were evaluated to obtain summary estimates regarding their associations with AD. In total, the data from 24 studies (2611 patients with AD and 2822 control subjects from 23 provinces and special districts in China) that were obtained from the Chinese Biomedicine Database, China National Knowledge Infrastructure, PubMed, and Medline were included. Different models (i.e., dominant, recessive, etc.) of these polymorphisms were analyzed using the Cochrane Review Manager. Statistically significant associations among patients with AD for the 1/1 genotype of the PS1 1/2 polymorphism [odds ratio (OR) = 1.77, 95% confidence interval (CI) = 1.03-3.04; P = 0.04] and the I/I genotype of the ACE I/D polymorphism (OR = 2.44, 95%CI = 1.78-3.35; P < 0.01) were identified. Statistically significant associations were also found for the PS1 1/2 polymorphism in both the dominant and recessive genetic models, whereas no association was found for the LRP C/T polymorphism. All studies exhibited heterogeneity (P < 0.05). This meta-analysis suggests that the 1/1 genotype of the PS1 1/2 polymorphism and the I/I genotype of the ACE I/D polymorphism are significantly associated with an increased risk of AD in the Chinese population.

show abstract

“…In addition, several adaptor and scaffold proteins, including Dab-1, potentially bind the cytoplasmic NPxY motifs of LRP and, although biochemical and physiological details are incomplete, numerous regulatory functions are suggested, including mitogen-activated protein (MAP) kinase signalling, ion channel function, microtubular transport, and axon guidance [41,44,45]. Genetic association studies suggest a direct link between LRP and AD, as the C766T polymorphism in exon 3 of LRP is under-represented [46]. However, although brains of AD patients with CT or TT genotypes contain higher levels of LRP [47] and circumstantial evidence suggests that LRP promotes Aß clearance [48], the relationship remains controversial [49].…”

Section: Discussionmentioning

confidence: 99%

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Thilakawardhana

Everett

Murdock

et al. 2005

Neurobiology of Aging

View full text Add to dashboard Cite

Apolipoprotein (apo) E4 is a risk factor for Alzheimer's disease, compared to wild-type apoE3. The mechanism(s) is unknown. One possibility, demonstrated in peripheral tissue cell lines, is that apoE stimulates nitric oxide synthase (NOS) via a receptor-dependent signalling pathway and that apoE4 generates inappropriate amounts of NO compared to apoE3. Prior to biochemical investigations, we have quantified the expression of several candidate receptor genes, including low-density lipoprotein (LDL)-receptor family members and scavenger receptor class B, types I and II (SR-BI/II), as well as the three NOS isoenzymes and protein kinase B (Akt), in 38 human cell lines, of which 12 derive from brain. Expression of apoE receptor 2 (apoER2), a known signalling receptor in brain, was readily detected in SH-SY-5Yand CCF-STTG1 cells, common models of neurons and astrocytes, respectively, and was highest in H4 neuroglioma and IMR-32 neuroblastoma cells. Transcripts of the other lipoprotein receptors were widely, but variably, distributed across the different cell types. Of particular note was the predominant expression of SR-BII over SR-BI in many of the brainderived cells. As the C-terminus of SR-BII, like apoER2, contains potential SH3 signalling motifs, we suggest that in brain SR-BII functions as a signal transducer receptor.

show abstract

Case-control study and meta-analysis of low density lipoprotein receptor-related protein gene exon 3 polymorphism in Alzheimer's disease

Cited by 45 publications

References 16 publications

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Islet-brain1/C-Jun N-terminal kinase interacting protein-1 (IB1/JIP-1) promoter variant is associated with Alzheimer's disease

Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer’s disease in the Chinese population: a meta-analysis of case-control studies

Quantification of apolipoprotein E receptors in human brain-derived cell lines by real-time polymerase chain reaction

Contact Info

Product

Resources

About