Genetic variation in the GCG and in the GLP1R genes and antipsychotic-induced weight gain.

Aim: GLP-1 plays a key role in glucose metabolism and influences antipsychotic-induced weight gain (AIWG). Our study is the first to investigate the encoding gene, GCG, and the GLP-1 receptor gene, GLP1R, and association with AIWG.

Materials & Methods: In 216 schizophrenic patients treated with antipsychotics for up to 14 weeks, we investigated four GCG and 33 GLP1R polymorphisms. Statistical analyses were conducted using SPSS, Haploview 4.2, UNPHASED 3.1.4 and the R-package mbmdr.

Results: We observed association of rs13429709 near GCG with AIWG (p(corr) = 0.044) in patients of European ancestry receiving olanzapine or clozapine (n = 87). We also found significant gene-gene interaction between rs13429709 and rs2268639 in GLP1R. Only nonsignificant trends were observed for GLP1R polymorphisms with AIWG.

Conclusion: We found significant association of rs13429709 with AIWG. Although there was no significant finding for GLP1R, the observed trends and interaction suggest this to be an interesting gene for further examination.