Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit

Gutteridge, Timothy; Kumaran, Mahalakshmi; Ghosh, Sunita; Fainsinger, Robin L.; Klepstad, Pål; Tarumi, Yoko; Damaraju, Sambasivarao; Baracos, Vickie E.

doi:10.1016/j.jpainsymman.2018.07.011

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…Interestingly, TAOK2 was found to be recruited to the internalization vacuole containing intracellular bacteria in Listeria monocytogenes infected cells and involved in regulation of vacuolar rupture and cytoplasmic access of these bacteria [ 73 ]. Genetic variations in the TAOK3 locus rs795484 were reported to be associated with increased morphine requirement in children of European Caucasian ancestry and with increased acute postoperative pain in both European Caucasian and African American subjects [ 74 , 75 ], although the underlying mechanism is unknown and requires further determination [ 76 ]. It has been proposed that TAOK3 may act as a pharmacogene that affects the response to analgesic treatment [ 77 ].…”

Section: Tao Kinases In Other Physiological Processes and Diseasesmentioning

confidence: 99%

The Diverse Roles of TAO Kinases in Health and Diseases

Fang

Lai

Hsiao

et al. 2020

IJMS

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Thousand and one kinases (TAOKs) are members of the MAP kinase kinase kinase (MAP3K) family. Three members of this subfamily, TAOK1, 2, and 3, have been identified in mammals. It has been shown that TAOK1, 2 and 3 regulate the p38 MAPK and Hippo signaling pathways, while TAOK 1 and 2 modulate the SAPK/JNK cascade. Furthermore, TAOKs are involved in additional interactions with other cellular proteins and all of these pathways modulate vital physiological and pathophysiological responses in cells and tissues. Dysregulation of TAOK-related pathways is implicated in the development of diseases including inflammatory and immune disorders, cancer and drug resistance, and autism and Alzheimer’s diseases. This review collates current knowledge concerning the roles of TAOKs in protein–protein interaction, signal transduction, physiological regulation, and pathogenesis and summarizes the recent development of TAOK-specific inhibitors that have the potential to ameliorate TAOKs’ effects in pathological situations.

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Section: Tao Kinases In Other Physiological Processes and Diseasesmentioning

confidence: 99%

The Diverse Roles of TAO Kinases in Health and Diseases

Fang

Lai

Hsiao

et al. 2020

IJMS

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“…Individual SNP associations are not necessarily responsible for phenotype; causal SNPs could be in linkage disequilibrium with those studied. Finally, we expect that rare variants and additional GWAS-identified loci, such as TAOK3 , now showing increased importance across other clinical pain and analgesia phenotypes, 63 will become essential components of larger and more precise genetic testing arrays for morphine analgesia and acute postoperative pain.…”

Section: Discussionmentioning

confidence: 99%

Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits

Wei

Zhang

et al. 2019

Pharmacogenomics J

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Acute pain and opioid analgesia demonstrate inter-individual variability and polygenic influence. In 241 children of African American and 277 of European Caucasian ancestry, we sought to replicate select candidate gene associations with morphine dose and postoperative pain and then to estimate dose prediction limits. Twenty-seven single nucleotide polymorphisms (SNPs) from 9 genes ( ABCB1, ARRB2, COMT, DRD2, KCNJ6, MC1R, OPRD1, OPRM1, UGT2B7 ) met selection criteria and were analyzed along with TAOK3 . Few associations replicated: morphine dose (mcg/kg) in African American children and ABCB1 rs1045642 (A allele, ß=−9.30, 95% CI −17.25–−1.35, p=0.02) and OPRM1 rs1799971 (G allele, ß=23.19, 95% CI 3.27–43.11, p=0.02); KCNJ6 rs2211843 and high pain in African American subjects (T allele, OR 2.08, 95% CI 1.17–3.71, p=0.01) and in congruent European Caucasian pain phenotypes; and COMT rs740603 for high pain in European Caucasian subjects (A allele, OR 0.69, 95% CI 0.48–0.99, p=0.046). With age, body mass index, and physical status as covariates, simple top SNP candidate gene models could explain theoretical maximums of 24.2% (European Caucasian) and 14.6% (African American) of morphine dose variances.

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“…In another GWAS study, TAOK3 was identified as a genetic predisposition to loneliness (Abdellaoui et al, 2019), a status that accompanies NDDs (Kwan et al, 2020;Papagavriel et al, 2020). In addition, two independent GWAS analyses showed that TAOK3 is related to high opioid requirement for patients with advanced cancer pain (Gutteridge et al, 2018) and morphine requirement for postoperative pain in a retrospective pediatric day surgery population (Cook-Sather et al, 2014), suggesting a functional role of TAOK3 in controlling pain under certain conditions. Since the impairment of sensory perception/processing is highly associated with NDDs, like autism (Robertson and Baron-Cohen, 2017), the possible function of TAOK3 in NDDs is further implied.…”

Section: Taok3mentioning

confidence: 99%

Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

Pan

Yang

et al. 2021

Front. Mol. Neurosci.

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Despite the complexity of neurodevelopmental disorders (NDDs), from their genotype to phenotype, in the last few decades substantial progress has been made in understanding their pathophysiology. Recent accumulating evidence shows the relevance of genetic variants in thousand and one (TAO) kinases as major contributors to several NDDs. Although it is well-known that TAO kinases are a highly conserved family of STE20 kinase and play important roles in multiple biological processes, the emerging roles of TAO kinases in neurodevelopment and NDDs have yet to be intensively discussed. In this review article, we summarize the potential roles of the TAO kinases based on structural and biochemical analyses, present the genetic data from clinical investigations, and assess the mechanistic link between the mutations of TAO kinases, neuropathology, and behavioral impairment in NDDs. We then offer potential perspectives from basic research to clinical therapies, which may contribute to fully understanding how TAO kinases are involved in NDDs.

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Single-Nucleotide Polymorphisms in TAOK3 Are Associated With High Opioid Requirement for Pain Management in Patients With Advanced Cancer Admitted to a Tertiary Palliative Care Unit

Cited by 10 publications

References 23 publications

The Diverse Roles of TAO Kinases in Health and Diseases

The Diverse Roles of TAO Kinases in Health and Diseases

Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits

Clinical and Neurobiological Aspects of TAO Kinase Family in Neurodevelopmental Disorders

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