rs3851179 Polymorphism at 5′ to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population

Santos-Rebouças, Cíntia Barros; Gonçalves, Andressa Pereira; Santos, J. M.; Abdala, Bianca Barbosa; Motta, Luciana Branco da; Laks, Jérson; Borges, Margarete Borges de; Rosso, Ana Lucia; Pereira, Joäo Santos; Nicaretta, Denise Hack; Pimentel, Márcia Mattos Gonçalves

doi:10.1007/s12017-017-8444-z

Cited by 20 publications

(29 citation statements)

References 41 publications

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“…hsa_circ_0023919 is located in PICALM gene that is involved in clathrin-mediated endocytosis at neuromuscular junctions [26] and single nucleotide polymorphism upstream of the gene has been associated with Alzheimer’s disease [40]. This circRNA was downregulated in microarray analysis and qPCR results also confirmed this.…”

Section: Discussionmentioning

confidence: 83%

Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis

et al. 2019

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Circular RNAs (circRNAs) are emerging as a novel, yet powerful player in many human diseases. They are involved in several cellular processes and are becoming a noteworthy type of biomarkers. Among other functions, circRNAs can serve as RNA sponges or as scaffolds for RNA-binding proteins. Here, we investigated a microarray expression profile of circRNAs in leukocyte samples from ALS patients and age- and sex-matched healthy controls to identify differentially expressed circRNAs. We selected 10 of them for a qPCR validation of expression on a larger set of samples, identification of their associations with clinical parameters, and evaluation of their diagnostic potential. In total, expression of 7/10 circRNAs was significant in a larger cohort of ALS patients, compared with age- and sex-matched healthy controls. Three of them (hsa_circ_0023919, hsa_circ_0063411, and hsa_circ_0088036) showed the same regulation as in microarray results. These three circRNAs also had AUC > 0.95, and sensitivity and specificity for the optimal threshold point > 90%, showing their potential for using them as diagnostic biomarkers.

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Section: Discussionmentioning

confidence: 83%

Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis

et al. 2019

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“…Furthermore, most studies have focused on the role of PICALM in PD; however, none were able to investigate the effect of this gene on cognitive impairment 13,16‐18 . Santos‐Rebouças and colleagues 13 performed a case‐control study in a Brazilian population of 174 patients with late‐onset AD, 166 patients with late‐onset PD, and 176 controls and showed that the rs3851179 T allele represented a significant protective factor for PD with an OR similar to AD. Nonetheless, the plausible interaction of PICALM and APOE was only assessed in the AD cohort.…”

Section: Discussionmentioning

confidence: 99%

“…The PICALM gene encodes the clathrin adaptor protein involved in clathrin‐mediated endocytosis, which is an essential step in the intracellular trafficking of proteins, lipids, growth factors, and neurotransmitters. In recent years, the potential role of PICALM rs3851179 in the pathogenesis of PD has been assessed using ethnically diverse study populations, but the findings have been mixed 13‐18 …”

Section: Introductionmentioning

confidence: 99%

Association of PICALM with Cognitive Impairment in Parkinson's Disease

et al. 2020

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Background Cognitive impairment is one of the most disabling nonmotor symptoms in Parkinson's disease (PD). Recently, a genome‐wide association study in Alzheimer's disease has identified the PICALM rs3851179 polymorphism as one of the most significant susceptibility genes for Alzheimer's disease after APOE. The aim of this study was to determine the potential role of PICALM and its genetic interaction with APOE in the development of cognitive decline in PD. Methods A discovery cohort of 712 patients with PD were genotyped for PICALM (rs3851179) and APOE (rs429358 and rs7412) polymorphisms. The association of PICALM and APOE–PICALM genetic interaction with cognitive dysfunction in PD was studied using logistic regression models, and the relationship of PICALM with cognitive decline onset was assessed with Cox regression analysis. PICALM effect was then replicated in an international, independent cohort (Parkinson's Progression Markers Initiative, N = 231). Results PICALM rs3851179 TT genotype was significantly associated with a decreased risk of cognitive impairment in PD (TT vs. CC + CT, P = 0.041, odds ratio = 0.309). Replication studies further demonstrated its protective effect on cognitive impairment in PD. In addition, the protective effect of the PICALM rs3851179 TT genotype was more pronounced in the APOE ε4 (−) carriers from the discovery cohort (P = 0.037, odds ratio = 0.241), although these results were not replicated in the Parkinson's Progression Markers Initiative cohort. Conclusions Our results support the fact that PICALM is associated with cognitive impairment in PD. The understanding of its contribution to cognitive decline in PD could provide new targets for the development of novel therapies. © 2020 International Parkinson and Movement Disorder Society

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“… 31 2017 Colombia Mixed population (Caucasian, African and American) 280 357 PCR C/T Santos-Reboucas et al . 32 2017 Brazil Mixed population (Caucasian, African and mulatto) 174 175 TaqMan CC/CT/TT Ferrari et al . 15 2012 UK Mixed population (Caucasian and African) 342 277 TaqMan C/T Gu et al .…”

Section: Methodsmentioning

confidence: 99%

Analyzing 74,248 Samples Confirms the Association Between CLU rs11136000 Polymorphism and Alzheimer’s Disease in Caucasian But Not Chinese population

Han

Zhao

et al. 2018

Sci Rep

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Clusterin (CLU) is considered one of the most important roles for pathogenesis of Alzheimer’s Disease (AD). The early genome-wide association studies (GWAS) identified the CLU rs11136000 polymorphism is significantly associated with AD in Caucasian. However, the subsequent studies are unable to replicate these findings in different populations. Although two independent meta-analyses show evidence to support significant association in Asian and Caucasian populations by integrating the data from 18 and 25 related GWAS studies, respectively, many of the following 18 studies also reported the inconsistent results. Moreover, there are six missed and a misclassified GWAS studies in the two meta-analyses. Therefore, we suspected that the small-scale and incompletion or heterogeneity of the samples maybe lead to different results of these studies. In this study, large-scale samples from 50 related GWAS studies (28,464 AD cases and 45,784 controls) were selected afresh from seven authoritative sources to reevaluate the effect of rs11136000 polymorphism to AD risk. Similarly, we identified that the minor allele variant of rs11136000 significantly decrease AD risk in Caucasian ethnicity using the allele, dominant and recessive model. Different from the results of the previous studies, however, the results showed a negligible or no association in Asian and Chinese populations. Collectively, our analysis suggests that, for Asian and Chinese populations, the variant of rs11136000 may be irrelevant to AD risk. We believe that these findings can help to improve the understanding of the AD’s pathogenesis.

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rs3851179 Polymorphism at 5′ to the PICALM Gene is Associated with Alzheimer and Parkinson Diseases in Brazilian Population

Cited by 20 publications

References 41 publications

Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis

Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis

Association of PICALM with Cognitive Impairment in Parkinson's Disease

Analyzing 74,248 Samples Confirms the Association Between CLU rs11136000 Polymorphism and Alzheimer’s Disease in Caucasian But Not Chinese population

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