title: TNF-α -308 G>A polymorphism and weight gain in patients with schizophrenia under long-term clozapine, risperidone or olanzapine treatment.
abstract: Atypical or second-generation antipsychotics (SGAs) are associated with excessive body weight gain (BWG) and other components of metabolic syndrome. Among all SGAs, clozapine and olanzapine are known to cause the most significant weight gain, followed by risperidone and quetiapine. The genetic variant of tumor necrosis factor α (TNF-α), -308 G>A polymorphism (rs1800629), has been implicated in clozapine-induced BWG in several studies. We hypothesized that TNF-α -308 G>A polymorphism has a general effect on SGA-induced BWG. The present study was conducted to examine the association between TNF-α -308 G>A polymorphism and BWG during treatment for schizophrenia using a variety of second generation antipsychotics (SGAs). A total of 500 patients with schizophrenia treated with clozapine (n=275), olanzapine (n=79) or risperidone (n=146) for an average of 49.9 months were recruited. Subjects with an increase in weight of more than 7% from the baseline before the current SGA treatment to the weight at the survey point were defined as having BWG. The association between TNF-α -308 G>A polymorphism and BWG was studied, and the effect of non-genetic factors such as baseline BMI, SGA treatment duration and SGA type on the association was controlled by logistic regression. The results revealed that there was no significant association between BWG and TNF-α -308 G>A polymorphism (GG/GA/AA or GG/GA+AA) in each separate SGA group or collectively. These findings suggest that TNF-α -308 G>A polymorphism does not play a major role in SGA-induced weight gain.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsiang-Hsuan
authors.initials: HH
authors.lastname: Huang
authors.forename: Ying-Chieh
authors.initials: YC
authors.lastname: Wang
authors.forename: Chia-Liang
authors.initials: CL
authors.lastname: Wu
authors.forename: Chen-Jee
authors.initials: CJ
authors.lastname: Hong
authors.forename: Ya-Mei
authors.initials: YM
authors.lastname: Bai
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
authors.forename: Ying-Jay
authors.initials: YJ
authors.lastname: Liou
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D003024:Clozapine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D016037:Single-Blind Method; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics*
chemical_list: D014150:Antipsychotic Agents; D014409:Tumor Necrosis Factor-alpha; D001569:Benzodiazepines; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine