C825T polymorphism of the GNB3 gene on valproate-related metabolic abnormalities in bipolar disorder patients.
BACKGROUND
Valproate (VPA) is a mood stabilizer for treating patients with bipolar disorder (BD). It may cause metabolic abnormalities in certain bipolar patients. However, the genetic factors that influence the susceptibility remain unclear. Genetic polymorphism of the G-protein β3 subunit (GNB3) is reported to be associated with metabolic phenotypes. In the current study, we investigated the possible associations between the GNB3 variation and VPA-induced metabolic abnormalities.


METHODS
Subjects (n = 96) who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BD were recruited from the National Cheng Kung University Hospital. Their metabolic indices were measured.


RESULTS
The variation of GNB3 C825T showed an association with higher plasma total cholesterol (P = 0.037), triglyceride (P = 0.014), and leptin (P < 0.001) levels in BD patients treated with VPA. After adjusting for age, sex, types of BDs, and serum concentration of VPA, the variation of GNB3 C825T remained significantly associated with the levels of serum leptin and body mass index (BMI; P < 0.001 and P = 0.030, respectively). In addition, the GNB3 C825T showed significant drug-single-nucleotide polymorphism interactions with insulin levels (P = 0.033), triglyceride levels (P = 0.013), leptin levels (P = 0.013), and BMI (P = 0.018). These results indicated that the T allele may be associated with lower serum leptin levels and BMI in BD patients treated with VPA.


CONCLUSIONS
The current study provides evidence that BD patients who are T allele carriers of the GNB3 C825T polymorphism have a lower risk for VPA-induced metabolic abnormalities. Further studies about the underlying mechanisms of G protein in VPA-induced metabolic abnormalities are warranted.
Chang
Hui Hua
HH
Institute of Biopharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.
Gean
Po Wu
PW
Chou
Chen Hsi
CH
Yang
Yen Kuang
YK
Tsai
Hsin Chun
HC
Lu
Ru Band
RB
Chen
Po See
PS
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D006580:Genetic Carrier Screening; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D014635:Valproic Acid / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D055815:Young Adult
C454420:G-protein beta3 subunit; D020738:Leptin; D021122:Protein Subunits; D014635:Valproic Acid; D020962:Heterotrimeric GTP-Binding Proteins