Lack of association of CR1, PICALM and CLU gene polymorphisms with Alzheimer disease in a Polish population

Klimkowicz‐Mrowiec, Aleksandra; Sado, Małgorzata; Dziubek, Anna; Dziedzic, Tomasz; Pera, Joanna; Szczudlik, Andrzej; Słowik, Agnieszka

doi:10.5114/ninp.2013.33825

Cited by 20 publications

(20 citation statements)

References 11 publications

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“…Similar negative results in the Polish population were obtained in studies of CR1, PICALM and CLU gene polymorphisms [12]. Therefore the slightly positive results obtained in studies by Bednarska-Makaruk et al [4] are very interesting.…”

Section: Discussionsupporting

confidence: 70%

Original article On the lack of a clear-cut association between alpha-2-macroglobulin deletion and the risk of Alzheimer disease in Poland

Michałowska-Wender

Wawrzynek²,

G³

et al. 2014

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A b s t r a c t Alzheimer disease (AD) is a complex, multi-factorial disease with the potential involvement of several genes. Alpha-2-macroglobulin (A2M) has been implicated in AD on the basis of its ability to mediate the clearance and degradation of β-amyloid peptide. Nevertheless, it is not clear whether there are racial differences in frequency of polymorphisms of A2M in AD. We examined a group of 50 unrelated patients from Poland (38 women and 12 men), who were diagnosed clinically as probably developing AD (according to the N1NCD3 -ADR PA criteria). The patients were examined by a neurologist and a psychologist and had a CT or MRI scan of the brain. Fifty individuals of matched age, withoutany signs of dementia, were studied as a control group. DNA was extracted by a routine method from a blood sample. Amplification and genotyping at A2M was performed as described by Blacker et al. (1997). The genotypic distribution in A2M exon 18 in patients with AD and genotype TT in A2M exon 24 was similar to that in the controls. Significant differences were noted only in early onset AD in males and for old onset disease in females. The deletions were found more frequently in AD; however, they were found in only a small proportion of studied patients. These findings indicate that A2M is not the only biological candidate gene for AD determination.

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Section: Discussionsupporting

confidence: 70%

Original article On the lack of a clear-cut association between alpha-2-macroglobulin deletion and the risk of Alzheimer disease in Poland

Michałowska-Wender

Wawrzynek²,

G³

et al. 2014

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“…Two SNPs (rs3851179 and rs541458) 5′ to the PICALM gene were identified to be associated with reduced LOAD risk in Caucasians ( Harold et al, 2009 ; Lambert et al, 2009 ; Lambert et al, 2013 ). However, the reproducibility of these results was questionable when ethnic factor was taken into account ( Li et al, 2011 ; Klimkowicz-Mrowiec et al, 2013 ; Tan L. et al, 2013 ). Genetic heterogeneity may be the underlying reason at play.…”

Section: Cell Adhesion and Endocytosismentioning

confidence: 97%

“…Meta analysis show that SNPs rs11136000, rs2279590, rs7012010, rs7982, and rs9331888 in CLU are protective genetic factors in LOAD 3 . However, the reproducibility of these associations was questionable when ethnic factors were taken into account ( Li et al, 2011 ; Klimkowicz-Mrowiec et al, 2013 ; Tan L. et al, 2013 ). Genetic heterogeneity may be the underlying cause at play.…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Disease: From Genetic Variants to the Distinct Pathological Mechanisms

Sun

Xie

Tang

et al. 2017

Front. Mol. Neurosci.

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Being the most common cause of dementia, AD is a polygenic and neurodegenerative disease. Complex and multiple factors have been shown to be involved in its pathogenesis, of which the genetics play an indispensable role. It is widely accepted that discovery of potential genes related to the pathogenesis of AD would be of great help for the understanding of neurodegeneration and thus further promote molecular diagnosis in clinic settings. Generally, AD could be clarified into two types according to the onset age, the early-onset AD (EOAD) and the late-onset AD (LOAD). Progresses made by genetic studies on both EOAD and LOAD are believed to be essential not only for the revolution of conventional ideas but also for the revelation of new pathological mechanisms underlying AD pathogenesis. Currently, albeit the genetics of LOAD is much less well-understood compared to EOAD due to its complicated and multifactorial essence, Genome-wide association studies (GWASs) and next generation sequencing (NGS) approaches have identified dozens of novel genes that may provide insight mechanism of LOAD. In this review, we analyze functions of the genes and summarize the distinct pathological mechanisms of how these genes would be involved in the pathogenesis of AD.

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“…Of the 33 studies summarized in Table 1, 25 studies either include or exclusively focus on the impact of the rs11136000 SNP on AD risk; however, the results are inconsistent. Thirteen studies conclude that possession of rs11136000 does confer increased AD risk [26,27,[68][69][70][71][72][73][74][75][76][77], while ten studies conclude no significant association between rs11136000 and AD [78][79][80][81][82][83][84][85]. Moreover, two studies conclude that possession of the rs11136000 SNP reduces risk of AD development [86,87].…”

Section: Clu Polymorphisms In Loadmentioning

confidence: 99%

Clusterin (APOJ) in Alzheimer’s Disease: An Old Molecule with a New Role

Woody¹,

Zhao²

2016

Update on Dementia

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Clusterin (CLU), initially identified in 1983 as a "clustering factor" in ram rete testis fluid, is a multifaceted protein that was rediscovered and subsequently renamed eight times from 1983 to 1992. CLU exists as multiple protein isoforms including the 80 kDa glycosylated mature/secreted form of CLU (mCLU) and the smaller non-modified nuclear and intracellular forms of CLU (nCLU and icCLU, respectively). These isoforms, which are expressed at the highest levels in the brain, are suggested to play distinct roles in various disease processes such as those involving inflammation and apoptosis. Currently, CLU, also known as apolipoprotein J (APOJ) which belongs to the same protein family as apolipoprotein E (APOE), is the third most significant genetic risk factor for the development of late-onset Alzheimer's disease (LOAD); however, an extensive gap exists in the literature in understanding the physiological roles of CLU in normal brain and the pathogenic mechanisms conferred by CLU polymorphisms in the onset of LOAD. In this chapter, we discuss the status of the current knowledge regarding the generation and regulation of CLU protein isoforms, the clinical evidence and possible mechanisms involved in LOAD, and provide our perspectives for future studies.

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Lack of association of CR1, PICALM and CLU gene polymorphisms with Alzheimer disease in a Polish population

Abstract: Our results suggest that investigated SNPs are not associated with AD in a Polish population.

Cited by 20 publications

References 11 publications

Original article On the lack of a clear-cut association between alpha-2-macroglobulin deletion and the risk of Alzheimer disease in Poland

Original article On the lack of a clear-cut association between alpha-2-macroglobulin deletion and the risk of Alzheimer disease in Poland

Alzheimer’s Disease: From Genetic Variants to the Distinct Pathological Mechanisms

Clusterin (APOJ) in Alzheimer’s Disease: An Old Molecule with a New Role

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