Tags

Type your tag names separated by a space and hit enter

Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results.
PLoS One 2013; 8(8):e72652Plos

Abstract

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.

Authors+Show Affiliations

Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23967328

Citation

Zhang, Yi, et al. "Association Study of Val66Met Polymorphism in Brain-derived Neurotrophic Factor Gene With Clozapine-induced Metabolic Syndrome: Preliminary Results." PloS One, vol. 8, no. 8, 2013, pp. e72652.
Zhang Y, Chen M, Wu Z, et al. Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. PLoS ONE. 2013;8(8):e72652.
Zhang, Y., Chen, M., Wu, Z., Chen, J., Yu, S., Fang, Y., & Zhang, C. (2013). Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. PloS One, 8(8), pp. e72652. doi:10.1371/journal.pone.0072652.
Zhang Y, et al. Association Study of Val66Met Polymorphism in Brain-derived Neurotrophic Factor Gene With Clozapine-induced Metabolic Syndrome: Preliminary Results. PLoS ONE. 2013;8(8):e72652. PubMed PMID: 23967328.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association study of Val66Met polymorphism in brain-derived neurotrophic factor gene with clozapine-induced metabolic syndrome: preliminary results. AU - Zhang,Yi, AU - Chen,Meijuan, AU - Wu,Zhiguo, AU - Chen,Jun, AU - Yu,Shunying, AU - Fang,Yiru, AU - Zhang,Chen, Y1 - 2013/08/13/ PY - 2013/05/20/received PY - 2013/07/12/accepted PY - 2013/8/23/entrez PY - 2013/8/24/pubmed PY - 2014/5/16/medline SP - e72652 EP - e72652 JF - PloS one JO - PLoS ONE VL - 8 IS - 8 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/23967328/Association_study_of_Val66Met_polymorphism_in_brain_derived_neurotrophic_factor_gene_with_clozapine_induced_metabolic_syndrome:_preliminary_results_ L2 - http://dx.plos.org/10.1371/journal.pone.0072652 DB - PRIME DP - Unbound Medicine ER -