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.
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.
1 Department of Oriental Rehabilitation, Gangnam Korean Hospital, Kyunghee University , Seoul, Korea.
Junghyun
J
Park
Shambhunath
S
Bose
Sun-Woo
SW
Hong
Dong-Ki
DK
Lee
Jae-Wook
JW
Yoo
Chi-Yeon
CY
Lim
Myeongjong
M
Lee
Hojun
H
Kim
D020413:3' Untranslated Regions; D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D015992:Body Mass Index; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000188:drug therapy* / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D010919:Placebos; D020641:Polymorphism, Single Nucleotide; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics; D056910:Republic of Korea; D000071246:Uncoupling Protein 2; D055105:Waist Circumference
D020413:3' Untranslated Regions; C568534:ADRB3 protein, human; D019440:Anti-Obesity Agents; D004365:Drugs, Chinese Herbal; C454420:G-protein beta3 subunit; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047495:PPAR gamma; D010919:Placebos; D022702:Receptors, Adrenergic, beta-3; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; C098310:bofu-tsusho-san; D020962:Heterotrimeric GTP-Binding Proteins
Bofutsushosan; clinical trial; obesity; single nucleotide polymorphism