Fat-mass and obesity-associated gene polymorphisms and weight gain after risperidone treatment in first episode schizophrenia

Abstract

BackgroundObesity induced by antipsychotics severely increases the risk of many diseases and significantly reduces quality of life. Genome Wide Association Studies has identified fat-mass and obesity-associated (FTO) gene associated with obesity. The relationship between the FTO gene and drug-induced obesity is unclear.MethodTwo hundred and fifty drug naïve, Chinese Han patients with first-episode schizophrenia were enrolled in the study, and genotyped for four single nucleotide polymorphisms (SNPs rs9939609, rs8050136, rs1421085 and rs9930506) by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. Body weight and body mass index (BMI) were measured at baseline and six months after risperidone treatment.ResultsAt baseline, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609; body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After 6 months of risperidone treatment, body weight and BMI of TT homozygotes were lower than those of A allele carriers in rs9939609 (p’s <0.01); body weight and BMI of CC homozygotes were lower than those of A allele carriers in rs8050136 (p’s < 0.05); body weight of AA homozygotes was higher than those of G allele carriers in rs9930506 (p’s < 0.05). After controlling for age, gender, age of illness onset, disease duration, weight at baseline and education, weight gain of TT homozygotes at 6 months remained to be lower than those of A allele carriers in rs9939609 (p < 0.01); weight gain of CC homozygotes at 6 months was lower than those of A allele carriers in rs8050136 (p = 0.01). Stepwise multiple regression analysis suggested that, among 4 SNPs, rs9939609 was the strongest predictor of weight gain after 6 months of risperidone treatment (p = 0.001).ConclusionsThe FTO gene polymorphisms, especially rs9939609, seem to be related to weight gain after risperidone treatment in Chinese Han patients with first episode schizophrenia.

Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated with Second-Generation Antipsychotic-Induced Weight Gain

“…Another reason might be the small body weight of the group of heterozygotes at the beginning of the study as a low BMI is suggested to be a risk factor for weight gain under antipsychotic pharmacotherapy [28]. Our results agree with the findings of Song et al, who showed a significant effect on weight gains for rs9939609 A-allele carriers [18]. However, both study populations differ from each other.…”

“…This SNP is considered clearly associated with obesity, and its role in SGA-induced weight gain has already been characterized in different data sets. While some studies reported of a correlation between rs9939609 and SGA-induced weight gain, other studies did not find any significant effect [18][19][20][21][22]. Despite these contradictory results, FTO seems to be a high-potential candidate contributing to variations in SGA-induced weight gain and requiring further investigation.…”

Genetics of second-generation antipsychotic and mood stabilizer-induced weight gain in bipolar disorder

“…Given their promising role in body weight control, these four SNPs have been investigated for a possible association with AIWG by recent studies [54,55] and the rs9939609 polymorphism has been associated with this phenotype by multiple independent observations [39,55,56]. In our study, no effect on weight gain has been found for rs9939609 and rs8050136, whereas rs1421085 was not available in the STEP-BD genome-wide database.…”

Haloperidol and Risperidone at high concentrations activate an in vitro inflammatory response of RAW 264.7 macrophage cells by induction of apoptosis and modification of cytokine levels

“…After stimulating the cells with haloperidol, clozapine, quetiapine, and risperidone, the authors found that all antipsychotic drugs reduced interferon-γ (IFN-γ) levels and increased IL-10 levels, indicating their anti-inflammatory effect. However, in the more recent investigation performed by Song et al (2014), risperidone treatment initially produced an anti-inflammatory effect that became less pronounced as the treatment progressed. The authors postulated that alterations in the inflammatory metabolism associated with antipsychotic use could be actually attributed to the weight gain, as one of the treatment side effects.…”