Weight gain associated with the α_2a-adrenergic receptor -1291 C/G polymorphism and olanzapine treatment

Weight gain can be an adverse effect of antipsychotics and is an important factor for long-term health and treatment compliance. Many reports have shown that the α₂-adrenergic receptor may be related to eating behaviors or lipolytic activities, both associated with body weight change. We hypothesized that there might be a relationship between the α _2a-adrenergic receptor -1291 C/G polymorphism and olanzapine-induced weight gain. A group of 62 Korean schizophrenic patients participated in a study; weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the -1291 C/G polymorphism was performed on all participants. Body weight changes from baseline to endpoint were significantly associated with genotypes (P = 0.028). The frequency of the G allele was significantly higher in subjects who had severe weight gain (defined as a more than 10% weight gain from baseline) compared to subjects who did not have extreme weight gain (less than 10% weight gain from baseline) (X² = 6.120, P = 0.013; OR = 2.58, 95% CI = 1.21-5.51). Therefore, the findings from this study support a relationship between the -1291 C/G polymorphism of the α_2a-adrenergic receptor and weight gain in Korean schizophrenic patients receiving olanzapine treatment.