PMID- 23967328
OWN - NLM
STAT- MEDLINE
DCOM- 20140514
LR  - 20220410
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 8
DP  - 2013
TI  - Association study of Val66Met polymorphism in brain-derived neurotrophic factor 
      gene with clozapine-induced metabolic syndrome: preliminary results.
PG  - e72652
LID - 10.1371/journal.pone.0072652 [doi]
LID - e72652
AB  - The prevalence of the metabolic syndrome (MetS) is higher among patients 
      receiving atypical antipsychotics (AAPs) treatment, and even among AAPs, 
      treatment with clozapine has been shown to be associated with a higher long-term 
      incidence rate of MetS. Likewise, brain-derived neurotrophic factor (BDNF) 
      deficiency has been reported to result in metabolic traits, such as increased 
      food intake, hyperphagia and obesity, etc. In this study, we hypothesized that a 
      functional polymorphism (Val66Met) in the BDNF gene may confer susceptibility to 
      clozapine-induced MetS, potentially in a sex-specific manner, since an 
      interaction between Val66Met polymorphism and sex was observed in our previous 
      studies. A total of 199 schizophrenia patients being treated with clozapine were 
      divided into two groups, MetS and non-MetS, based on the diagnostic criteria of 
      the National Cholesterol Education Program's Adult Treatment Panel III. We 
      genotyped the Val66Met polymorphism, and measured the serum levels of fasting 
      glucose (GLU), triglyceride (TG) and high density lipoprotein cholesterol (HDL). 
      There was a trend indicating a significant association between the homozygous 
      Met/Met genotype and MetS in male patients (OR = 2.39; 95% CI: 1.05-5.41; 
      p = 0.039; corrected p = 0.078). Among the six risk factors listed in the ATPIII 
      criteria, we found a significant association between fasting GLU levels and 
      Val66Met polymorphism in males (p = 0.005; corrected p = 0.03), but not in 
      females (p = 0.65). Post-hoc analysis in males revealed that the Met/Met carriers 
      had significant higher levels of fasting GLU than those with Val/Val or Val/Met 
      genotypes (p = 0.007; corrected p = 0.042 and p = 0.002; corrected p = 0.012, 
      respectively). In conclusion, we observed a weak association between the Val66Met 
      polymorphism and clozapine-induced MetS in a sex-specific manner. While 
      preliminary, such findings prompt further, large-scale longitudinal studies to 
      replicate these findings.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong 
      University School of Medicine, Shanghai, China.
FAU - Chen, Meijuan
AU  - Chen M
FAU - Wu, Zhiguo
AU  - Wu Z
FAU - Chen, Jun
AU  - Chen J
FAU - Yu, Shunying
AU  - Yu S
FAU - Fang, Yiru
AU  - Fang Y
FAU - Zhang, Chen
AU  - Zhang C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130813
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Codon)
RN  - 0 (Serotonin Antagonists)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Alleles
MH  - *Amino Acid Substitution
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Clozapine/adverse effects
MH  - *Codon
MH  - Cross-Sectional Studies
MH  - Female
MH  - Genetic Association Studies
MH  - Genotype
MH  - Humans
MH  - Male
MH  - Metabolic Syndrome/chemically induced/*genetics
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Serotonin Antagonists/adverse effects
PMC - PMC3742721
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/08/24 06:00
MHDA- 2014/05/16 06:00
PMCR- 2013/08/13
CRDT- 2013/08/23 06:00
PHST- 2013/05/20 00:00 [received]
PHST- 2013/07/12 00:00 [accepted]
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
PHST- 2013/08/13 00:00 [pmc-release]
AID - PONE-D-13-20783 [pii]
AID - 10.1371/journal.pone.0072652 [doi]
PST - epublish
SO  - PLoS One. 2013 Aug 13;8(8):e72652. doi: 10.1371/journal.pone.0072652. eCollection 
      2013.