Evidence map›Paper›PMID 25740917›Full record

ArticleThe international journal of neuropsychopharmacology2015

Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid.

Hongliang Li, Xueding Wang, Yafang Zhou, Guanzhong Ni, Qibiao Su, Ziyi Chen, Zhuojia Chen, Jiali Li, Xinmeng Chen, Xiangyu Hou and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The international journal of neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.6field-weighted citation impact, top 6% of its field
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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

18 citing papers in PubMed, 51 citations in OpenAlex.

  1. Mechanisms of weight gain associated with valproic acid: a scoping review.European archives of psychiatry and clinical neuroscience · 2026
    Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. A Longitudinal Study of the Association between theInternational journal of molecular sciences · 2022
    Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Pharmacogenomics in epilepsy.Neuroscience letters · 2018
    Review
  17. The pharmacogenomics of valproic acid.Journal of human genetics · 2017
    Review
  18. Article
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

14 authors at 3 institutions in 1 country.

Hongliang LiInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Xueding WangInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Yafang ZhouInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Guanzhong NiInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Qibiao SuInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Ziyi ChenInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Zhuojia ChenInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Jiali LiInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Xinmeng ChenInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Xiangyu HouInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Wen XieInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Shuang XinInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Liemin ZhouInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie).
Min HuangInstitute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Drs H Li, Wang, Y Zhou; Zhuojia Chen, J Li, X Chen, Hou, Xin, and Huang); The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China (Drs Ni, Ziyi Chen, and L Zhou); Guangdong Pharmaceutical University, Guangzhou, China (Dr Su); Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Xie). huangmin@mail.sysu.edu.cn lmzhou56@163.com.
Guangdong Pharmaceutical University · CNSun Yat-sen University · CNThe First Affiliated Hospital, Sun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWeight gain is the most frequent adverse effect of valproic acid (VPA) treatment, resulting in poor compliance and many endocrine disturbances. Similarities in the weight change of monozygotic twins receiving VPA strongly suggests that genetic factors are involved in this effect. However, few studies have been conducted to identify the relevant genetic polymorphisms. Additionally, the causal relationship between the VPA concentration and weight gain has been controversial. Thus, we investigated the effects of single nucleotide polymorphisms (SNPs) in several appetite stimulation and energy homeostasis genes and the steady state plasma concentrations (Css) of VPA on the occurrence of weight gain in patients.

methodsA total of 212 epilepsy patients receiving VPA were enrolled. Nineteen SNPs in 11 genes were detected using the Sequenom MassArray iPlex platform, and VPA Css was determined by high-performance liquid chromatography (HPLC).

resultsAfter 6 months of treatment, 20.28% of patients were found to gain a significant amount of weight (weight gained ≥7%). Three SNPs in the leptin receptor (LEPR), ankyrin repeat kinase domain containing 1 (ANKK1), and α catalytic subunit of adenosine monophosphate-activated protein kinase (AMPK) showed significant associations with VPA-induced weight gain (p < 0.001, p = 0.017 and p = 0.020, respectively). After Bonferroni correction for multiple tests, the genotypic association of LEPR rs1137101, the allelic association of LEPR rs1137101, and ANKK1 rs1800497 with weight gain remained significant. However, the VPA Css in patents who gained weight were not significantly different from those who did not gain weight (p = 0.121).

conclusionsLEPR and ANKK1 genetic polymorphisms may have value in predicting VPA-induced weight gain.

Indexed as

AdolescentAdultAMP-Activated Protein KinasesAnticonvulsantsBody WeightChromatography, High Pressure LiquidEpilepsyFemaleGenetic Predisposition to DiseaseHumansMalePolymorphism, Single NucleotideProtein Serine-Threonine KinasesReceptors, LeptinValproic AcidWeight GainAMP-Activated Protein KinasesANKK1 protein, humanAnticonvulsantsLEPR protein, humanProtein Serine-Threonine KinasesReceptors, LeptinValproic Acidconcentrationpolymorphismvalproic acidweight gain

Identifiers

PMID25740917
PMCPMC4540110
OpenAlexW2101360984

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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 OpenQuestion graph.