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Analysis of institutional authors

Mejía-Abril G.AuthorMejía-Abril, GinaAuthorZubiaur PCorresponding Author
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Clinical relevance of novel polymorphisms in the dihydropyrimidine dehydrogenase (Dpyd) gene in patients with severe fluoropyrimidine toxicity: A spanish case-control study

Publicated to:Pharmaceutics. 13 (12): - 2021-12-01 13(12), DOI: 10.3390/pharmaceutics13122036

Authors: Soria-Chacartegui P; Villapalos-García G; López-Fernández LA; Navares-Gómez M; Mejía-Abril G; Abad-Santos F; Zubiaur P

Affiliations

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas , Hospital Universitario de la Princesa - Author
Hosp Gen Univ Gregorio Maranon, IiSGM, Madrid 28007, Spain - Author
Hospital Universitario de la Princesa - Author
Inst Salud Carlos III, CIBERehd, Madrid 28029, Spain - Author
Instituto de Investigación Sanitaria Gregorio Marañón - Author
Univ Autonoma Madrid, Inst Invest Sanitaria La Princesa IP, Inst Teofilo Hernando, Clin Pharmacol Dept,La Princesa Univ Hosp, Madrid 28029, Spain - Author
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Abstract

Among cancer patients treated with fluoropyrimidines, 10–40% develop severe toxicity. Polymorphism of the dihydropyrimidine dehydrogenase (DPYD) gene may reduce DPD function, the main enzyme responsible for the metabolism of fluoropyrimidines. This leads to drug accumulation and to an increased risk of toxicity. Routine genotyping of this gene, which usually includes DPYD *HapB3, *2A, *13 and c.2846A > T (D949V) variants, helps predict approximately 20–30% of toxicity cases. For DPD intermediate (IM) or poor (PM) metabolizers, a dose adjustment or drug switch is warranted to avoid toxicity, respectively. Societies such as the Spanish Society of Pharmacogenetics and Pharmacogenomics (SEFF), the Dutch Pharmacogenetics Working Group (DPWG) or the Clinical Pharmacogenetics Implementation Consortium (CPIC) and regulatory agencies (e.g., the Spanish Medicines Agency, AEMPS) already recommend DPYD routine genotyping. However, the predictive capacity of genotyping is currently still limited. This can be explained by the presence of unknown polymorphisms affecting the function of the enzyme. In this case-control work, 11 cases of severe fluoropyrimidine toxicity in patients who did not carry any of the four variants mentioned above were matched with 22 controls, who did not develop toxicity and did not carry any variant. The DPYD exome was sequenced (Sanger) in search of potentially pathogenic mutations. DPYD rs367619008 (c.187 A > G, p.Lys63Glu), rs200643089 (c.2324 T > G, p.Leu775Trp) and rs76387818 (c.1084G > A, p.Val362Ile) increased the percentage of explained toxicities to 38–48%. Moreover, there was an intronic variant considered potentially pathogenic: rs944174134 (c.322-63G > A). Further studies are needed to confirm its clinical relevance. The remaining variants were considered non-pathogenic.

Keywords
5-fluorouracilcapecitabinechemotherapydeficiencydihydropyrimidine dehydrogenase (dpyd)genotypepharmacogeneticspolymorphism5-fluorouracilCapecitabineDihydropyrimidine dehydrogenase (dpyd)PharmacogeneticsPolymorphismVariants

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Pharmaceutics due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 39/279, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 2.64, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-02, the following number of citations:

  • WoS: 7
  • Scopus: 9
  • OpenCitations: 8
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 16.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 16 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.95.
  • The number of mentions on the social network X (formerly Twitter): 4 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Soria-Chacartegui P) and Last Author (ZUBIAUR PRECIOSO, PABLO).

the authors responsible for correspondence tasks have been Abad-Santos F and ZUBIAUR PRECIOSO, PABLO.