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Cited by 24Alzheimer's disease research and treatmentsGenomics and Rare DiseasesGenetic Associations and Epidemiology

Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer’s Disease

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Masoodi, Tariq Ahmad, Al Shammari, Sulaiman A., Al-Muammar, May N., Alhamdan, Adel A.·2012·Neurology Research International
DOI 10.1155/2012/480609PMC PMC3317072
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Abstract

Introduction. Apolipoprotein E (APOE) is an important risk factor for Alzheimer’s disease (AD) and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs) are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene.Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns) SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server.Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs) score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD) values were higher for three mutant-type structures compared to the native modeled structure.Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

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  • The 10 listed APOE variants (p.Arg50Cys, p.Thr60Ala, p.Pro102Gln, p.Ala117Thr, p.Arg132Ser, p.Glu139Val, p.Glu150Gly, p.Arg152Gln, p.Glu189Lys, and p.Gln205Arg) have only been analyzed in silico for APOE SNPs.

    “have only been analyzed in silico for APOE SNPs and their clinical data were unknown (Table 5)126).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [126]

    The Methods and Results (sections 3.1–3.5) describe computational analysis of APOE SNPs, supporting the in-silico characterization. The passages do not identify the ten variants by the listed amino-acid changes or establish that they had only been analyzed in silico; they also do not state that clinical data for those variants were unknown. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • The clinical data for the 10 listed APOE variants (p.Arg50Cys, p.Thr60Ala, p.Pro102Gln, p.Ala117Thr, p.Arg132Ser, p.Glu139Val, p.Glu150Gly, p.Arg152Gln, p.Glu189Lys, and p.Gln205Arg) were unknown.

    “have only been analyzed in silico for APOE SNPs and their clinical data were unknown (Table 5)126).”

    From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [126]

    The Methods and Results describe computational analyses of APOE SNPs, supporting the statement that the paper analyzed variants in silico. But the passages in our copy do not identify the ten listed amino-acid variants or state that their clinical data were unknown; the Results’ reference to an unknown risk score for ten SNPs is not a statement about clinical data. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 35

  1. [1]Strittmatter W Roses AD Apolipoprotein E and Alzheimer disease Proceedings of the National Academy of Sciences of the United States of America 1995 92 4725 4727 7761390 PMC41779
  2. [2]Corder E Saunders A Strittmatter W Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families Science 1993 261 5123 921 923 8346443
  3. [3]Kwon OD Khaleeq A Chan W Pavlik VN Doody RS Apolipoprotein e polymorphism and age at onset of Alzheimer's disease in a quadriethnic sample Dementia and Geriatric Cognitive Disorders 2011 30 6 486 491 21252542
  4. [4]Roses AD Apolipoprotein E alleles as risk factors in Alzheimer’s disease Annual Review of Medicine 1996 47 387 400 8712790
  5. [5]Weisgraber K Mahley R Human apolipoprotein E: the Alzheimer’s disease connection The FASEB Journal 1996 10 13 1485 1494 8940294
  6. [6]Mauch DH Nägier K Schumacher S CNS synaptogenesis promoted by glia-derived cholesterol Science 2001 294 5545 1354 1357 11701931
  7. [7]Roheim PS Carey M Forte T Vega GL Apolipoproteins in human cerebrospinal fluid Proceedings of the National Academy of Sciences of the United States of America 1979 76 9 4646 4649 291993 PMC411636
  8. [8]Dieter LS Estus S Isoform of APOE with retained intron 3; quantitation and identification of an associated single nucleotide polymorphism Molecular Neurodegeneration 2010 5 1, article 34 PMC2940878 20822524
  9. [9]Rajasekaran R Sudandiradoss C Doss CG Sethumadhavan R Identification and in silico analysis of functional SNPs of the BRCA1 gene Genomics 2007 90 4 447 452 17719744
  10. [10]Fredman D Siegfried M Yuan YP Bork P Lehväslaiho H Brookes AJ HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources Nucleic Acids Research 2002 30 1 387 391 11752345 PMC99093
  11. [11]Smigielski EM Sirotkin K Ward M Sherry ST dbSNP: a database of single nucleotide polymorphisms Nucleic Acids Research 2000 28 1 352 355 10592272 PMC102496
  12. [12]Barroso I Gurnell M Crowley VE Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension Nature 1999 402 6764 880 883 10622252
  13. [13]Thomas R McConnell R Whittacker J Kirkpatrick P Bradley J Sandford R Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR American Journal of Human Genetics 1999 65 1 39 49 10364515 PMC1378073
  14. [14]Yoshida A Huang IY Ikawa M Molecular abnormality of an inactive aldehyde dehydrogenase variant commonly found in Orientals Proceedings of the National Academy of Sciences of the United States of America 1984 81 1 258 261 6582480 PMC344651
  15. [15]Jaruzelska J Abadie V d’Aubenton-Carafa Y Brody E Munnich A Marie J In vitro splicing deficiency induced by a C to T mutation at position -3 in the intron 10 acceptor site of the phenylalanine hydroxylase gene in a patient with phenylketonuria Journal of Biological Chemistry 1995 270 35 20370 20375 7657610
  16. [16]Johnson MM Houck J Chen C Screening for deleterious nonsynonymous single-nucleotide polymorphisms in genes involved in steroid hormone metabolism and response Cancer Epidemiology Biomarkers and Prevention 2005 14 5 1326 1329 15894696
  17. [17]Doss CG Sethumadhavan R Investigation on the role of nsSNPs in HNPCC genes—a bioinformatics approach Journal of Biomedical Science 2009 16 1, article 42 PMC2682794 19389263
  18. [18]Capriotti E Fariselli P Casadio R I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure Nucleic Acids Research 2005 33 2 306 310 PMC1160136 15980478
  19. [19]Ng PC Henikoff S Predicting deleterious amino acid substitutions Genome Research 2001 11 5 863 874 11337480 PMC311071
  20. [20]Altschul SF Madden TL Schäffer AA Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Nucleic Acids Research 1997 25 17 3389 3402 9254694 PMC146917
  21. [21]Sjölander K Karplus K Brown M Dirichlet mixtures: a method for improved detection of weak but significant protein sequence homology Computer Applications in the Biosciences 1996 12 4 327 345 8902360
  22. [22]Xi T Jones IM Mohrenweiser HW Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function Genomics 2004 83 6 970 979 15177551
  23. [23]Ramensky V Bork P Sunyaev S Human non-synonymous SNPs: server and survey Nucleic Acids Research 2002 30 17 3894 3900 12202775 PMC137415
  24. [24]Yuan HY Chiou JJ Tseng WH FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization Nucleic Acids Research 2006 34 W635 W641 16845089 PMC1538865
  25. [25]Arnold K Bordoli L Kopp J Schwede T The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling Bioinformatics 2006 22 2 195 201 16301204
  26. [27]Laskowski RA Rullmann JA MacArthur MW Kaptein R Thornton JM AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR Journal of Biomolecular NMR 1996 8 4 477 486 9008363
  27. [28]Bowie JU Luthy R Eisenberg D A method to identify protein sequences that fold into a known three-dimensional structure Science 1991 253 5016 164 170 1853201
  28. [29]Lindahl E Azuara C Koehl P Delarue M NOMAD-Ref: visualization, deformation and refinement of macromolecular structures based on all-atom normal mode analysis Nucleic Acids Research 2006 34 W52 W56 16845062 PMC1538881
  29. [30]Ramachandran GN Ramakrishnan C Sasisekharan V Stereochemistry of polypeptide chain configurations Journal of Molecular Biology 1963 7 95 99 13990617
  30. [31]Delarue M Dumas P On the use of low-frequency normal modes to enforce collective movements in refining macromolecular structural models Proceedings of the National Academy of Sciences of the United States of America 2004 101 18 6957 6962 15096585 PMC406448
  31. [32]Han JH Kerrison N Chothia C Teichmann SA Divergence of interdomain geometry in two-domain proteins Structure 2006 14 5 935 945 16698554
  32. [33]Varfolomeev SD Uporov IV Fedorov EV Bioinformatics and molecular modeling in chemical enzymology. Active sites of hydrolases Biochemistry 2002 67 10 1099 1108 12460108
  33. [34]Ng PC Henikoff S Accounting for human polymorphisms predicted to affect protein function Genome Research 2002 12 3 436 446 11875032 PMC155281
  34. [35]George Priya Doss C Rajasekaran R Sudandiradoss C Ramanathan K Purohit R Sethumadhavan R A novel computational and structural analysis of nsSNPs in CFTR gene Genomic Medicine 2008 2 1-2 23 32 18716917 PMC2518663
  35. [36]Zhu Y Spitz MR Amos CI Lin J Schabath MB Wu X An evolutionary perspective on single-nucleotide polymorphism screening in molecular cancer epidemiology Cancer Research 2004 64 6 2251 2257 15026370

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Authors
Masoodi, T. A., Al Shammari, S. A., Al-Muammar, M. N., & Alhamdan, A. A.
Affiliations
  • King Saud University (SA)
  • Health Care Development for Elderly Research Chair, Community Health Sciences Department, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh 11433, Saudi Arabia
Corresponding author
Masoodi, Tariq Ahmad
ORCID
Venue
Neurology Research International
Publisher
Wiley
Published
2012
Volume
2012
Pages
1-8
ISSN
  • 2090-1852 (ISSN-L)
  • 2090-1860
DOI
10.1155/2012/480609
PMC
PMC3317072
OpenAlex
W2053954955
Cited by
24
References
0
Citations by year
2025: 3 · 2024: 4 · 2023: 2 · 2022: 1 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2013: 3
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurology Research International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
King Saud University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
APOE gene, Alzheimer's disease, non-synonymous single nucleotide polymorphisms, deleterious mutations, protein stability, genetic risk, late-onset Alzheimer's disease, protein structure modeling

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