Navigating the Cyp2 Gene Family Research Landscape:

A Comprehensive Bibliometric Analysis

Kristiadi Priambodo

, Jefman Efendi Marzuki HY

, Risma Ikawaty

Baharuddin

and Salsa Bella Destri Syafika

Bachelor of Medicine Program,

Medical Faculty, University of Surabaya, Surabaya, 60293, Indonesia

Faculty of Medicine, University of Surabaya, Surabaya, 60293, Indonesia

Keywords: Mapping of Science, CYP2 Gene, Precision Medicine, Bibliometrik.

Abstract: This study elucidates the role of the CYP2 gene family in the pharmacokinetics and pharmacodynamics of

drugs. The variability in these genes significantly influences drug efficacy and individual response. With the

increasing volume of scientific publications, a comprehensive understanding of the current research on the

CYP2 gene family is crucial. Numerous studies have examined these genetic variations, yet a thorough

assessment of this research landscape and the identification of unexplored areas are still needed. Through

bibliometric analysis and global mapping, this study enables a more systematic interpretation of publication

data, offering new insights. The aim is to perform scientific mapping and interpretation of the CYP2 gene

family research corpus. Utilizing literature review methods and bibliometric analysis based on PRISMA

guidelines, a search in the Scopus database with the keyword cyp2* yielded 11,867 articles. After cleaning

and preparation, 9,439 articles remained for analysis. The results indicate a significant increase in CYP2 gene

research, particularly between 2012-2023. Mapping reveals five main clusters, with CYP2E1 and CYP2D6

as the largest. CYP2C9 stands out for its polarization with three other clusters, indicating strong research

collaboration. Identified strategic areas include opioids, atrial fibrillation, PCI, DNA methylation,

hepatocellular carcinoma, and bile acid. Key genes in polymorphism studies include CYP2C19 and CYP2C8,

while CYP2D6 is crucial in drug monitoring. This science mapping provides essential insights for research

development in precision medicine.

1 INTRODUCTION

The CYP2 gene family holds significant importance

in the field of medicine, particularly in the study of

pharmacokinetics and pharmacodynamics of drugs.

Genes such as CYP2C9, CYP2C19, and CYP2C16

influence how drugs are metabolized in the body

(pharmacokinetics), which can affect the

effectiveness of how drugs interact with their

biological targets (pharmacodynamics) (Gong et al.,

2023). For example, variations in these genes can

impact the efficacy of drugs like warfarin, with

certain genetic variants increasing the risk of side

effects. Although research has deepened our

understanding of these genes, there is a need to assess

the entire research landscape and identify areas that

are not yet fully explored. With the growing number

of scientific publications, it is essential to have a

Corresponding author

comprehensive understanding of how research

related to the CYP2 gene family has evolved.

Understanding the "mapping of science" in this field

will not only reveal current trends but also identify

knowledge gaps that may not have been recognized.

This is crucial for maximizing the efficiency of

research efforts and directing resources to the most

needy or strategic areas. Bibliometric analysis, with

its ability to map and interpret publication data

systematically, offers a solution to this challenge. In

analyzing trends in the medical field, this tool has

been effectively used, such as in orthopedic therapy

studies (Jin et al., 2023). Although reviews on the

CYP2 family are still scarce, utilizing this analytical

approach makes exploration easier. Therefore, this

study aims to delve deeper into the research landscape

between topics, and highlight opportunities for future

research related to precision medicine.

278

Priambodo, K., HY, J. E. M., Ikawaty, R., Baharuddin, and Syaﬁka, S. B. D.

Navigating the Cyp2 Gene Family Research Landscape: A Comprehensive Bibliometric Analysis.

DOI: 10.5220/0013671400003873

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 1st International Conference on Medical Science and Health (ICOMESH 2023), pages 278-285

ISBN: 978-989-758-740-5

2 MATERIALS AND METHODS

This study adhered to the bibliometric research

guidelines established by Donthu (Donthu et al.,

2021). We methodically executed several steps to

maintain data accuracy and ensure exhaustive

reporting of findings. The research involved various

critical phases, starting with the formulation of the

research question, followed by the creation of a

controlled set of vocabulary and keywords. Following

this, the process included identifying references from

databases using specific filters, data preparation and

cleaning, performing mathematical analysis and

visualizations, and ultimately interpreting the

outcomes (Donthu et al., 2021). A strategic approach

for searching was developed to obtain the most

relevant and accurate documents. The keywords and

search queries used were:

Keyword 1: TITLE-ABS-KEY (cyp2*) AND gene

AND PUBYEAR > 2011 AND PUBYEAR < 2024

AND (LIMIT-TO (SRCTYPE, "j")) AND (LIMIT-

TO (PUBSTAGE, "final")) AND (LIMIT-TO

(DOCTYPE, "ar")) AND (LIMIT-TO (SUBJAREA,

"MEDI") OR LIMIT-TO (SUBJAREA, "PHAR")

OR LIMIT-TO (SUBJAREA, "BIOC") OR LIMIT-

TO (SUBJAREA, "CHEM") OR LIMIT-TO

(SUBJAREA, "NEUR") OR LIMIT-TO

(SUBJAREA, "IMMU") OR LIMIT-TO

(SUBJAREA, "NURS") OR LIMIT-TO

(SUBJAREA, "HEAL") OR LIMIT-TO

(SUBJAREA, "DENT") OR LIMIT-TO

(SUBJAREA, "MATH") OR LIMIT-TO

(SUBJAREA, "VETE") OR LIMIT-TO

(SUBJAREA, "COMP")) AND (LIMIT-TO

(LANGUAGE, "English"))

The article search was conducted on October 20,

2023, using the Scopus database. In this search, we

employed several filters to obtain relevant and precise

documents. The following is the scheme and some

filter limitations used in the search, as illustrated in

Figure 1. Research Questions RQ1 How many main

clusters are there in the CYP2 family studies? RQ2

What is the relationship among the clusters in the

CYP2 family? RQ3 What are the strategic topics in

the CYP2 family research? RQ4 Is there any

dynamics in the publication of the CYP2 family?

Figure 1: Document selection stages adapted from the PRISMA flow diagram (Page et al., 2021).

Topic Scope and Eligibility

Topic

Scope, Strategy and

Coverage

Record Identified From

Database (n= 11.867)

Screening

Record Screened

( n=11. 8 6 7 )

Record Assessed for

Eligibility (n= 9.439)

Included

Record Included for

Bibliometric Analysis

(n= 9.439)

CYP2 Family Gene

Database: Scopus

TITLE-ABS-KEY ( cyp2* ) AND gene AND PUBYEAR > 2011 AND PUBYEAR <

20 2 4 A N D ( LIMIT-TO ( SRCTYPE , "j" ) ) AN D ( LIMIT-TO ( PUBSTA GE ,

"final" ) ) AND ( LIMIT-TO ( DOCTYPE , "ar" ) ) AND ( LIMIT-TO ( SU BJAREA ,

"MEDI" ) OR LIMIT-TO ( SUBJAREA , "PHA R" ) OR LIMIT-TO ( SUBJAREA ,

"BIOC" ) OR LIMIT-TO ( SUBJAREA , "CHEM" ) OR LIMIT-TO ( SUBJAREA ,

"N EUR" ) OR LIMIT-TO ( SUBJAREA , "IMMU" ) O R LIMIT-TO ( SUBJAREA ,

"NURS" ) OR LIMIT-TO ( SUBJAREA , "HEAL" ) OR LIMIT-TO ( SUBJAREA ,

"DENT" ) OR LIMIT-TO ( SUBJAREA , "MATH" ) OR LIMIT-TO ( SUBJAREA ,

"VETE" ) OR LIMIT-TO ( SUBJAREA , "COMP" ) ) AND ( LIMIT-TO (

LANGUAGE , "Eng lish " ) )

Date: October 20, 2023

Record Exclude:

• No Article/Conference Paper/Book

Chapter/No Abstract/ No Author

Keyword (2384)

• Not in English (n=44)

Navigating the Cyp2 Gene Family Research Landscape: A Comprehensive Bibliometric Analysis

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3 RESULT AND DISCUSSION

3.1 Research Productivity

There are two main benchmarks for gauging the

productivity of research: the number of publications

and the number of citations, as both aspects are

closely related to the impact factor of research. The

higher the number of articles produced, the more

productive the researcher is in that field. In our

analysis of the CYP2 gene family, we observe a

significant increase in research outputs. A publication

momentum occurred in the period 2019-2022, where

publications exceeded the average of the previous 10

years, as seen in Figure 2.

According to the citation analysis, the countries

with the greatest impact are China and the United

States. In Asia, Japan represents the country with the

highest citation rate in CYP2 gene family studies.

This is understandable, given Japan's support from

various advanced technologies Figure 3.

Figure 2: Number of documents by year. Data sourced from Scopus.

Figure 3: Number of citations by country.

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3.2 CYP2 Gene Family Clusters

The optimized visualization of the CYP2 gene family

clusters reveals five primary clusters, distinguished

by different colors: red, green, blue, purple, and

yellow. The largest cluster is CYP2E1, colored red,

while the smallest is CYP2C19. As the largest cluster,

CYP2E1 is strongly associated with hepatotoxicity,

oxidative stress, and inflammation. There is also a

strong relationship between each topic in the CYP2

study. This section addresses RQ1-2 in this research

and is detailed further in the sub-studies. The

visualization also highlights strategic studies, which

are situated at the centrality with large nodes. In the

evolving research of the CYP2 gene family, there are

two aspects that consistently serve as bridges between

clusters, located centrally. The nodes acting as

bridges are metabolism and polymorphism Figure 4

and Figure 5.

Figure 4. Visualization of Global Co-occurrence of Topics Based on Author Keywords.

Figure 5. Visualization of Global Co-occurrence of Topics Based on Author Keywords and Cluster Areas.

Klaster utama

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3.3 The Role of CYP2 in Inflammation

Inflammation is a critical process in complex

biological systems, particularly in infection

conditions. It arises due to the body's response to

external antigens. CYP2E1 can metabolize

arachidonic acid into epoxyeicosatrienoic acids

(EETs), which have anti-inflammatory effects.

However, CYP2E1 is also known to produce reactive

oxygen species (ROS) as a by-product of metabolism,

which can contribute to oxidative stress and

inflammation. The stimulative effect of ROS has been

demonstrated by Abdelmeed and team, who proved

the role of CYP2E1 in non-alcoholic steatohepatitis

(NASH) (Abdelmegeed et al., 2012). Another

member, CYP2J2, also metabolizes arachidonic acid

into EETs, providing anti-inflammatory and

vasoprotective effects. Given the complexity of the

CYP2 gene family and its varied functions, these

genes play a significant role in both the promotion

and resolution of inflammation, depending on the

context and the specific CYP2 enzyme involved

Figure 6. Nevertheless, a serious concern is that the

regulation of oxidative stress can manifest as

hepatotoxicity (Jiang et al., 2021).

3.4 The Role of CYP2 in Polymorphism

Intensive research into polymorphisms is necessary to

provide evidence for the causes of drug metabolism

variation at the genomic level. However, monitoring

the direction of research development is crucial to

balancing the projection of where this research will

evolve. In this study, there are intriguing findings

regarding the CYP2 gene family and polymorphism.

Not all genes have the same weight in studies; not all

are strongly linked to polymorphism studies (Figure

4). In this study, the genes strongly associated with

genetic polymorphism are CYP24A1, CYP2C19,

CYP2D6, CYP2C9, and CYP2E1. In terms of

clusters, CYP24A1, as a centrality, has the most

distant relationship (green cluster) (Figure 7).

Figure 6. The Role of CYP2E1 in the Inflammation Process.

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Figure 7. Relationship of Genetic Polymorphism Studies to the CYP2 Gene Family.

In several studies, CYP24A1 is associated with

drugs like deferasirox, tenofovir disoproxil fumarate

(TDF), and telaprevir. Polymorphisms in CYP24A1

are presumed to be related to changes in the

pharmacokinetic profile of these drugs (Cusato et al.,

2015). There are 12 variant annotations recorded in

PharmGKB, of which 5 variants have clinical

annotations but with a level of evidence 3. This

indicates a lack of evidence linking CYP24A1

variants to changes in drug levels (CYP24A1, n.d.).

Furthermore, polymorphisms in CYP24A1 are not

yet listed in the Clinical Pharmacogenetics

Implementation Consortium (CPIC), suggesting

insufficient evidence of the effects of CYP24A1

variants on drugs (CPIC, 2023).

Interestingly, within the green cluster, the topic of

"smoking" is closely associated with genetic

polymorphism. The closest general clusters are

yellow, purple, and red. The closest topic is breast

cancer. Genetic polymorphisms often affect an

individual's susceptibility to breast cancer and their

response to treatment (Lum et al., 2013). For

example, certain genetic variations can affect drug

metabolism, impacting the efficacy and toxicity of

breast cancer therapies. Various studies have shown

the role of CYP2D6 in reducing the efficacy of

Tamoxifen (TMX) (Bezerra et al., 2018).

Additionally, genetic polymorphisms in genes related

to DNA repair, cell cycle, and hormonal pathways

can also affect the risk of developing breast cancer.

3.5 Therapeutic Drug Monitoring

Therapeutic drug monitoring (TDM) is a critical

component in assessing the effects of drugs on the

body. This examination allows for determining the

amount of drug exposure, thereby maintaining drug

levels within a therapeutic range (Voulgaridou et al.,

2023). Variations in the CYP2 genes can cause

changes in drug levels in the blood, leading to

variations and strategies in treatment. Numerous

studies have demonstrated the significant role of the

CYP2D6 gene in drug metabolism (De Rose et al.,

2020). In our analysis, there are 134 articles

discussing TDM. For example, TDM can be used for

dose optimization of the antidepressant escitalopram

(S-CIT) by understanding genetic variations in (Tsai

et al., 2010). In this study, we found 22 documents

discussing TDM and CYP2D6.

Navigating the Cyp2 Gene Family Research Landscape: A Comprehensive Bibliometric Analysis

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Figure 8. Research Trends of the CYP2 Gene Family.

3.6 CYP2 Family Research Trends

Research on the CYP2 family is focused on the

density of the P450 cluster. Identified strategic areas

include opioids, atrial fibrillation, PCI, DNA

methylation, hepatocellular carcinoma, and bile acid.

Several studies related to the CYP2D6 gene analyze

intermediate and poor metabolizers (IMs and PMs)

and pain management (Smith et al., 2019). The trend

node in the trend phase can be easily identified due to

its bright yellow visual (Figure 8).

4 CONCLUSIONS

The analysis of 9,439 articles related to the CYP2

gene family reveals a broad spectrum of study,

evidenced by the formation of five clusters: red,

green, yellow, blue, and purple. The inter-cluster

relationships are strong, as demonstrated by the

intersection of the purple and green clusters. Based on

the mapping, it is evident that the CYP2 genes play a

crucial role in drug metabolism, inflammation, and

drug monitoring.

ACKNOWLEDGEMENTS

The present study was funded by LPPM. We would

like to express our deepest gratitude to Lembaga

Penelitian dan Pengabdian kepada Masyarakat

(LPPM) Universitas Surabaya for their generous

support through the research funding scheme for

publication 2023. This financial support has been

instrumental in the realization of our research and its

dissemination.

Additionally, we extend our sincere thanks to the

Faculty of Medicine, Universitas Surabaya, for their

unwavering support and valuable contributions,

which have significantly facilitated the successful

completion of our research. Their guidance and

assistance have been crucial in achieving the

objectives of our study.

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