Population genetics of <i>PDE4B</i> (phosphodiesterase‐4B) in neglected Native Americans: Implications for cancer pharmacogenetics

Moreira, Rennan Garcias; Saraiva-Duarte, Julia Maria; Pereira, Alexandre C.; Sosa-Macías, Martha; Galavíz-Hernández, Carlos; Santolalla, Meddly L.; Magalhães, Wagner C. S.; Zolini, Camila; Leal, Thiago P.; Balázs, Zsolt; LLerena, Adrián; Gilman, Robert H.; Mill, José Geraldo; Borda, Víctor; Guio, Heinner; O’Connor, Timothy D.; Tarazona‐Santos, Eduardo; Rodrigues‐Soares, Fernanda

doi:10.1111/cts.13266

Cited by 6 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some population groups remain underrepresented in these types of investigations, such as Native American populations. Recently, some efforts have been made to include genetic information about allelic frequencies of Native American populations and their influence on susceptibility to diseases, such as severe forms of COVID-19 [ 23 ], psychological disorders [ 24 ], oncological diseases [ 25 , 26 ], and also on different types of pharmacological treatments [ 12 , 13 , 27 , 28 ]. Most of these studies are focused on one or a few group of genes.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Profile of Amazonian Amerindians

Rodrigues

Fernandes

Ribeiro-dos-Santos

et al. 2022

JPM

View full text Add to dashboard Cite

Given the role of pharmacogenomics in the large variability observed in drug efficacy/safety, an assessment about the pharmacogenomic profile of patients prior to drug prescription or dose adjustment is paramount to improve adherence to treatment and prevent adverse drug reaction events. A population commonly underrepresented in pharmacogenomic studies is the Native American populations, which have a unique genetic profile due to a long process of geographic isolation and other genetic and evolutionary processes. Here, we describe the pharmacogenetic variability of Native American populations regarding 160 pharmacogenes involved in absorption, distribution, metabolism, and excretion processes and biological pathways of different therapies. Data were obtained through complete exome sequencing of individuals from 12 different Amerindian groups of the Brazilian Amazon. The study reports a total of 3311 variants; of this, 167 are exclusive to Amerindian populations, and 1183 are located in coding regions. Among these new variants, we found non-synonymous coding variants in the DPYD and the IFNL4 genes and variants with high allelic frequencies in intronic regions of the MTHFR, TYMS, GSTT1, and CYP2D6 genes. Additionally, 332 variants with either high or moderate (disruptive or non-disruptive impact in protein effectiveness, respectively) significance were found with a minimum of 1% frequency in the Amazonian Amerindian population. The data reported here serve as scientific basis for future design of specific treatment protocols for Amazonian Amerindian populations as well as for populations admixed with them, such as the Northern Brazilian population.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Profile of Amazonian Amerindians

Rodrigues

Fernandes

Ribeiro-dos-Santos

et al. 2022

JPM

View full text Add to dashboard Cite

show abstract

“…ALL is characterized by an excess of immature lymphocytes, which are more common in children between the ages of 2 and 5 years than in adults ( Medinger et al, 2019 ). Rennan Garcias Moreira et al (2022) found that PDE4B promotes tumor angiogenesis in ALL. Notably, in Native Americans, the PDE4B allele rs6683977 variant is associated with ALL relapse ( Chen et al, 2020 ).…”

Section: Functional Regulatory Role Of Phosphodiesterase 4b In Human ...mentioning

confidence: 99%

The regulatory role of PDE4B in the progression of inflammatory function study

Ding²,

Yang³

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Inflammation is a response of the body to external stimuli (eg. chemical irritants, bacteria, viruses, etc.), and when the stimuli are persistent, they tend to trigger chronic inflammation. The presence of chronic inflammation is an important component of the tumor microenvironment produced by a variety of inflammatory cells (eg. macrophages, neutrophils, leukocytes, etc.). The relationship between chronic inflammation and cancer development has been widely accepted, and chronic inflammation has been associated with the development of many cancers, including chronic bronchitis and lung cancer, cystitis inducing bladder cancer. Moreover, chronic colorectitis is more likely to develop into colorectal cancer. Therefore, the specific relationship and cellular mechanisms between inflammation and cancer are a hot topic of research. Recent studies have identified phosphodiesterase 4B (PDE4B), a member of the phosphodiesterase (PDEs) protein family, as a major cyclic AMP (cAMP) metabolizing enzyme in inflammatory cells, and the therapeutic role of PDE4B as chronic inflammation, cancer. In this review, we will present the tumors associated with chronic inflammation, and PDE4B potential clinical application.

show abstract

A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations

Nasir,

Vinayagam,

Massi

et al. 2024

Molec Gen & Gen Med

View full text Add to dashboard Cite

BackgroundThis systematic review aims to highlight the scope of pharmacogenomics research within global Indigenous populations. This review also explores the barriers and facilitators of pharmacogenomics research within this population.MethodologyA systematic review of literature was conducted to identify and present an understanding of current empirical evidence demonstrating the conduct of genomics or pharmacogenomics research within global Indigenous populations (PROSPERO registration: CRD42021257226). Using key search terms, relevant databases were searched for articles published between January 2010 and July 2022. Screening, data extraction, and analysis was conducted using well‐defined inclusion criteria. Quality assessment and risk of bias appraisal was conducted using the mixed methods appraisal tool. Indigenous community engagement and participation in genomics research was assessed using the social‐ecological framework.ResultsFrom the 427 articles identified, 77 articles met inclusion criteria and underwent full‐text screening. Of these, 30 articles were included in the final review, with 16 being quantitative and 14 either qualitative or mixed methods studies. Most studies were conducted with native Indigenous populations from the United States of America (36%). Content analysis revealed that studies either explored genetic variations associated with disease in Indigenous populations (23%) or markers for drug metabolism (30%) or were designed to understand perspectives of genomics research within this population (47%). Perspectives included the exploration of the role of participants in research, benefits or outcomes achieved from participation in genomics research, and levels of Indigenous engagement and participation in genomics research.ConclusionsThis review highlights a growing gap in Indigenous genomics research globally. It presents several important considerations from Indigenous participants, identifying how researchers can co‐create culturally safe and inclusive design, implementation, analysis, and subsequent outcomes of genomics research involving Indigenous people. Indigenous governance, self‐determination and leadership is essential, with researchers required to be responsive to such fundamental partnerships for research to progress.

show abstract

Population genetics of PDE4B (phosphodiesterase‐4B) in neglected Native Americans: Implications for cancer pharmacogenetics

Abstract: PDE4B (phosphodiesterase-4B) has an important role in cancer and in pharmacology of some disorders, such as inflammatory diseases. Remarkably in Native | 1401 POPULATION GENETICS OF PDE4B IN NATIVE AMERICANS Federal do Triângulo Mineiro,

Cited by 6 publications

References 24 publications

Pharmacogenomic Profile of Amazonian Amerindians

Pharmacogenomic Profile of Amazonian Amerindians

The regulatory role of PDE4B in the progression of inflammatory function study

A Systematic Review Exploring Empirical Pharmacogenomics Research Within Global Indigenous Populations

Contact Info

Product

Resources

About