Evidence map›Paper›PMID 39555806›Full record

Trial reportPharmacogenomics2024

PPARA variant rs1800234 had a dose dependent pharmacogenetics impact on the therapeutic response to chiglitazar.

Zhaoxu Geng, Yuanting Zheng, Qian Li, Desi Pan, Xianping Lu, Fei Chen, Ying Zhang, Keying Li, Kaixin Zhou, Leming Shi and 1 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pharmacogenomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Zhaoxu GengInstitute of Biophysics, Chinese Academy of Sciences, Beijing, China.ORCID 0000-0001-6714-8382
Yuanting ZhengState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
Qian LiCollege of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Desi PanShenzhen Chipscreen Biosciences Co. Ltd, Shenzhen, Guangdong, China.
Xianping LuShenzhen Chipscreen Biosciences Co. Ltd, Shenzhen, Guangdong, China.
Fei ChenChina-Japan Friendship Hospital, Beijing, China.
Ying ZhangSchool of Clinical and Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Keying LiSchool of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Kaixin ZhouGuangzhou Laboratory, Guangzhou International Bio Island, Guangzhou, China.
Leming ShiState Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center, Fudan University, Shanghai, China.
You WangCenter for Translational Research, Shenzhen Bay Laboratory, Shenzhen, Guangdong, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOur objective was to explore the pharmacogenetic impact of three known functional variants in drug target genes and determine whether they can explain the inter-individual variation in therapeutic response.

methodsIn a post hoc analysis of data from randomized controlled clinical trials of chiglitazar, we genotyped 481 Chinese patients with T2DM and investigated the association of variants in PPAR genes with the therapeutic outcome separated by dose using linear regression.

resultsrs1800234, a gain-of-function variant of PPARA, had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. The C allele was significantly associated with reduced therapeutic response in the 48 mg group, while no significant association was observed in the 32 mg group. In addition, in patients without the C allele, patients treated with 48 mg chiglitazar had a better therapeutic response than those treated with 32 mg chiglitazar. To the contrary, in patients with the C allele, patients treated with 48 mg chiglitazar had a worse therapeutic response than those treated with 32 mg of chiglitazar.

conclusionThe PPARA variant rs1800234 had a dose-dependent pharmacogenetic impact on the therapeutic response to chiglitazar. It could help explain the absence of a dose effect of chiglitazar and serve as a potential biomarker for the chosen dose of chiglitazar in the future. In addition, our study provided important reference for the design and clinical application of multi-target drugs.

Indexed as

Dose-Response Relationship, DrugPharmacogeneticsPPAR alphaAgedAllelesEast Asian PeopleFemaleGenotypeHumansMaleMiddle AgedPolymorphism, Single NucleotideTreatment OutcomePPAR alphaPPARA protein, humanChiglitazardosepharmacogeneticsPPARrs1800234therapeutic response

Identifiers

PMID39555806
PMCPMC11703419

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.