Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients
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Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect.
The aim of this study was to investigate the association of selected single nucleotide polymorphisms (SNPs) of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor γ (PPARγ) with VPA-induced weight gain and obesity in epileptic patients.
A total of 225 Chinese Han epilepsy patients receiving VPA treatment were recruited in the study. Height and weight for the calculation of body mass index (BMI) were measured at the initiation of VPA therapy and in the follow-up examination. A BMI of 25 kg/m2 or higher was defined as obesity on the basis of the World Health Organization (WHO) criteria for Asian populations. Four SNPs in CD36 (rs1194197, rs7807607) and PPARγ (rs10865710, rs2920502) were genotyped using the Sequenom® MassArray iPlex platform.
About 19.6% of epileptic patients receiving VPA therapy were found to become obese. After covariate analysis of age, gender, sex, height, initial BMI, and VPA dosage, the CD36 rs1194197 C allele and rs7807607 T allele (OR, 0.31; 95%CI, 0.13–0.72; P = 0.009 and OR, 0.38; 95%CI; 0.18–0.83; P = 0.02, respectively) were identified as protective factors for VPA-induced obesity. The PPARγ rs10865710 C allele carriers were found to be less likely to suffer from VPA-induced obesity compared with GG genotype carriers (OR, 0.04; 95%CI, 0.01–0.12; P < 0.001). After a Bonferroni correction for multiple comparisons, the genotypic associations of CD36 rs1194197 and PPARγ rs10865710 and the allelic association of CD36 rs7807607 with obesity remained statistically significant.
Our data first indicated that CD36 and PPARγ polymorphisms may be associated with VPA-induced obesity and weight gain, suggesting that CD36 and PPARγ may have potential value in predicting VPA-induced obesity in Chinese Han epileptic patients.
KeywordsVPA Epileptic Obesity PPARγ CD36 Genetic polymorphisms
Prof. Min Huang and Prof. Jing Jin designed the research; Xupeng Bai and Dingsheng Wen performed the research; Chuncao Xu, Hongliang Li, and Yibei Chen assisted with the research; Prof. Min Huang, Prof. Prof. Xueding Wang, and Lie-min Zhou provided appreciated support for the acquisition of subjects. Xupeng Bai and Dingsheng Wen analyzed the data; Xupeng Bai and Prof. Jing Jin wrote the paper.
This work was supported by the National Key Research and Development Program (2017YFC0909303), National Natural Science Foundations of China [81730103 and 81573658], Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030], and the Science and Technology Planning Project of Guangdong Province (2017A020215147).
Compliance with ethical standards
This study was approved by the Human Investigation Ethics Committee of the School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (Clinicaltrials.gov Identifier No. NCT01172626). It was conducted in accordance with the Declaration of Helsinki and was consistent with applicable guidelines of good clinical practice.
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