Genetic polymorphisms of the beta2-adrenoceptor gene might influence metabolic disturbances during antipsychotic treatment

Novel antipsychotics are increasingly associated with metabolic disturbances and recent studies have shown a relation between a SNP in the 5-HT2C receptor gene and clozapine induced weight gain thus confirming that genetic factors might have an impact on this side effect.

We have genotyped 164 schizophrenic patients being treated with atypical neuroleptics for several polymorphisms in the ß1-, ß2- and ß3 receptor genes which are known to be involved in body weight and lipid metabolism. Weight, glucose and serum lipids have been monitored over a period of 5 weeks. Both, increase in weight (from 74 to 77kg; p=0.000) and in fasting glucose (p=0.000) were significant within the first weeks. The slight increase in cholesterol (from 187 to 212) and triglycerides (from 115 to 131) was not statistically significant. We found a significant relation between the ß2-AR Gly16Arg polymorphism and weight, as in Arg/Arg homozygotes weight gain was more pronounced (>4kg) than in Gly allele carriers (<1,5kg; p=0.009). We further found a correlation between this SNP and the basal cholesterol (254 vs. 185; p=0,000) and triglyceride levels (184 vs. 115; p=0.029).

Although still preliminary, our data are indicating that metabolic disturbances can be related to variants in genes other then the serotonergic ones. Although the overall deterioration in metabolic values were not pronounced within the first weeks, they might be indicative for the risk to develop the metabolic syndrome later on.