Association of MTHFR and PICALM polymorphisms with Alzheimer’s disease

Belcavello, Luciano; Camporez, Daniela; Almeida, Leila D.; Morelato, Renato Lírio; Batitucci, M. C. P.; Paula, Fabiana Martins de

doi:10.1007/s11033-014-3806-1

Cited by 13 publications

(10 citation statements)

References 37 publications

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“…Recently, an increasing number of studies have focused on the heritability of AD, as the classical amyloid hypothesis insufficiently explains the pathogenesis of AD (Hardy, 1997;Gatz et al, 2006). The identification of AD-susceptibility loci may, therefore, provide the basis for a helpful and complementary method for the timely and reliable diagnosis of this disease (Belcavello et al, 2015). Over the past few decades, genomewide association studies (GWAS), which overcome sample size limitations, were taken advantage of to study genetic changes that may contribute to AD.…”

Section: Introductionmentioning

confidence: 99%

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

Yan

Zhao

Qui

et al. 2020

Front. Aging Neurosci.

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Objectives: This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) within the southern Chinese population. Methods: A total of 420 participants, consisting of 215 AD patients and 205 sexand age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the apolipoprotein E (APOE) ε4 allele and age at onset, we performed an association analysis between these SNPs and AD susceptibility. Furthermore, we analyzed SNP-associated gene expression using the expression quantitative trait loci analysis. Results: Our study found that rs17125924 of FERMT2 was associated with the risk of developing AD in the dominant (P = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07-2.32) and overdominant (P = 0.005, OR = 1.76, 95% CI: 1.18-2.61) models. Moreover, compared with APOE ε4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in APOE ε4 allele carriers (P = 0.029). The rs9271058 of HLA-DRB1 (dominant, overdominant, and additive models), rs9473117 of CD2AP (dominant and additive models), and rs73223431 of PTK2B (dominant, overdominant, and additive models) were associated with early onset AD (EOAD). Using the genotype-tissue expression (GTEx) and Braineac database, we found a significant association between rs9271058 genotypes and HLA-DRB1 expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased CD2AP and PTK2B gene expression, respectively. Conclusion: Our study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in APOE ε4 carriers. In addition, we found that rs9271058 of HLA-DRB1, rs9473117 of CD2AP, and rs73223431 of PTK2B were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results.

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Section: Introductionmentioning

confidence: 99%

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

Yan

Zhao

Qui

et al. 2020

Front. Aging Neurosci.

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“… 51 2014 MCADRC African 44 223 TaqMan C/T Belcavello et al . 42 2015 Brazil American 81 161 PCR CC/CT/TT Moreno et al . 31 2017 Colombia Mixed population (Caucasian, African and American) 280 357 PCR C/T Santos-Reboucas 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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“…Genotyping was performed by our previous coworkers (Almada et al, 2012;Belcavello et al, 2015;dos Santos et al, 2016dos Santos et al, , 2017 using the Brazilian sample set of this study. The variant rs3764650 ABCA7 was performed by Santos et al (2017) through real time -polymerase chain reaction (qPCR), and the three standard genotypes were confirmed by Sanger sequencing.…”

Section: Blood Sampling and Genotypingmentioning

confidence: 99%

“…The variant rs3764650 ABCA7 was performed by Santos et al (2017) through real time -polymerase chain reaction (qPCR), and the three standard genotypes were confirmed by Sanger sequencing. Analysis of the variants rs744373 BIN1, rs11136000 CLU and (rs429358 and rs7412) APOE were performed, respectively, by Almada et al (2012), Belcavello et al (2015) and dos Santos et al (2016) thought restriction fragment length polymorphismpolymerase chain reaction (RFLP-PCR).…”

Section: Blood Sampling and Genotypingmentioning

confidence: 99%

“…The allelic combinations tested followed genes from lipid metabolism and the endocytosis pathway(ABCA7, CLU, BIN1and APOE). The allele frequencies of SNPs were inferred from the following studies: dosSantos et al (2017) for rs3764650 ABCA7; dosSantos et al (2016) for rs744373 BIN1,Belcavello et al (2015) for rs11136000 CLU, andAlmada et al (2012) for rs429358 and rs7412 APOE.…”

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confidence: 99%

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The combined risk effect among BIN1, CLU, and APOE genes in Alzheimer’s disease

et al. 2020

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Genome-wide associations studies (GWAS) are detecting new variants associated with late-onset of Alzheimer's disease (LOAD), a multifactorial neurodegenerative disorder. The variants rs744373 BIN1, rs11136000 CLU and rs3764650 ABCA7 uncovered by GWAS led to different AD pathways, such as metabolism, trafficking and endocytosis of lipids and inflammation. However, most of the association studies did not replicate these variants with significance. This could be due to a small power effect evident when these variants are tested independently with LOAD. Therefore, we aimed to investigate whether the combination of different variants would additively modify the risk of association with LOAD that is observed in GWAS. We performed an association study testing pairwise variants in metabolism, trafficking and endocytosis of lipid (rs429358 and rs7412 APOE, rs744373 BIN1, rs3764650 ABCA7 and rs11136000 CLU) pathways with LOAD in samples from southeastern Brazil. Our data suggest a risk effect for LOAD between APOE with CLU and APOE with BIN1 genes.

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Association of MTHFR and PICALM polymorphisms with Alzheimer’s disease

Cited by 13 publications

References 37 publications

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

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

The combined risk effect among BIN1, CLU, and APOE genes in Alzheimer’s disease

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