Impact of GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala polymorphisms on Bofutsushosan response in obese subjects: a randomized, double-blind, placebo-controlled trial

J Med Food. 2014 May;17(5):558-70. doi: 10.1089/jmf.2013.2836.


Obesity is known to be influenced by a number of genes, including the β3 subunit of G protein (GNB3), β3-adrenergic receptor (ADRB3), uncoupling protein 2 (UCP2), and peroxisome proliferator activated receptor gamma (PPARγ). The single nucleotide polymorphisms (SNPs) of the above genes, such as GNB3-C825T, ADRB3-Trp64Arg, UCP2-3'UTR 45 bp del/ins, and PPARγ-Pro12Ala, are associated with obesity and body mass index. The present study evaluates the impact of Bofutsushosan, a traditional Eastern Asian herbal medicine with known anti-obesity properties, on obese subjects according to the presence of the above-mentioned SNPs. Upon randomization, the volunteers were allocated to receive Bofutsushosan (n=55) or placebo (n=56) treatments for 8 weeks. Following the treatment schedule, significant reductions in total cholesterol and significant improvement in the Korean version of obesity-related quality of life scale were seen in the Bofutsushosan-treated group, but not in placebo. Bofutsushosan exerted significant anti-obesity effects on a number of parameters in the carriers of the GNB3-825T allele, but only on waist circumference in the GNB3-C/C homozygote. Significant anti-obesity impact of Bofutsushosan was also seen on a number of obesity-indices in both ADRB3-Arg64 carriers and ADRB3-Trp64 homozygotes, as well as in UCP2-D/D carriers, but not in UCP2-D/I+I/I variants. The effect of Bofutsushosan was more pronounced in PPARγ-Pro/Pro genotype compared to PPARγ-Pro/Ala variants. Thus, the results revealed differential responses of the subjects to the anti-obesity effects of Bofutsushosan treatment according to the polymorphism of the vital obesity-related genes. Our study provides new insight into individualized clinical applications of Bofutsushosan for obesity.

Keywords: Bofutsushosan; clinical trial; obesity; single nucleotide polymorphism.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Adult
  • Anti-Obesity Agents / therapeutic use*
  • Body Mass Index
  • Double-Blind Method
  • Drugs, Chinese Herbal / therapeutic use*
  • Genotype
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Humans
  • Ion Channels / genetics
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Mutation
  • Obesity / drug therapy*
  • Obesity / genetics*
  • PPAR gamma / genetics*
  • Placebos
  • Polymorphism, Single Nucleotide*
  • Receptors, Adrenergic, beta-3 / genetics
  • Republic of Korea
  • Uncoupling Protein 2
  • Waist Circumference


  • 3' Untranslated Regions
  • ADRB3 protein, human
  • Anti-Obesity Agents
  • Drugs, Chinese Herbal
  • G-protein beta3 subunit
  • Ion Channels
  • Mitochondrial Proteins
  • PPAR gamma
  • Placebos
  • Receptors, Adrenergic, beta-3
  • UCP2 protein, human
  • Uncoupling Protein 2
  • bofu-tsusho-san
  • Heterotrimeric GTP-Binding Proteins