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

BACKGROUND: Weight 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...

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Autores principales: Li, Hongliang, Wang, Xueding, Zhou, Yafang, Ni, Guanzhong, Su, Qibiao, Chen, Ziyi, Chen, Zhuojia, Li, Jiali, Chen, Xinmeng, Hou, Xiangyu, Xie, Wen, Xin, Shuang, Zhou, Liemin, Huang, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540110/
https://www.ncbi.nlm.nih.gov/pubmed/25740917
http://dx.doi.org/10.1093/ijnp/pyv021
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author Li, Hongliang
Wang, Xueding
Zhou, Yafang
Ni, Guanzhong
Su, Qibiao
Chen, Ziyi
Chen, Zhuojia
Li, Jiali
Chen, Xinmeng
Hou, Xiangyu
Xie, Wen
Xin, Shuang
Zhou, Liemin
Huang, Min
author_facet Li, Hongliang
Wang, Xueding
Zhou, Yafang
Ni, Guanzhong
Su, Qibiao
Chen, Ziyi
Chen, Zhuojia
Li, Jiali
Chen, Xinmeng
Hou, Xiangyu
Xie, Wen
Xin, Shuang
Zhou, Liemin
Huang, Min
author_sort Li, Hongliang
collection PubMed
description BACKGROUND: Weight 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. METHODS: A 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). RESULTS: After 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). CONCLUSIONS: LEPR and ANKK1 genetic polymorphisms may have value in predicting VPA-induced weight gain.
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spelling pubmed-45401102015-09-01 Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid Li, Hongliang Wang, Xueding Zhou, Yafang Ni, Guanzhong Su, Qibiao Chen, Ziyi Chen, Zhuojia Li, Jiali Chen, Xinmeng Hou, Xiangyu Xie, Wen Xin, Shuang Zhou, Liemin Huang, Min Int J Neuropsychopharmacol Research Article BACKGROUND: Weight 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. METHODS: A 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). RESULTS: After 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). CONCLUSIONS: LEPR and ANKK1 genetic polymorphisms may have value in predicting VPA-induced weight gain. Oxford University Press 2015-04-02 /pmc/articles/PMC4540110/ /pubmed/25740917 http://dx.doi.org/10.1093/ijnp/pyv021 Text en © The Author 2015. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Li, Hongliang
Wang, Xueding
Zhou, Yafang
Ni, Guanzhong
Su, Qibiao
Chen, Ziyi
Chen, Zhuojia
Li, Jiali
Chen, Xinmeng
Hou, Xiangyu
Xie, Wen
Xin, Shuang
Zhou, Liemin
Huang, Min
Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title_full Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title_fullStr Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title_full_unstemmed Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title_short Association of LEPR and ANKK1 Gene Polymorphisms with Weight Gain in Epilepsy Patients Receiving Valproic Acid
title_sort association of lepr and ankk1 gene polymorphisms with weight gain in epilepsy patients receiving valproic acid
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540110/
https://www.ncbi.nlm.nih.gov/pubmed/25740917
http://dx.doi.org/10.1093/ijnp/pyv021
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