The Role of Genetic Variation across IL-1B, IL-2, IL-6 and BDNF in Antipsychotic-Induced Weight Gain

Background: Antipsychotics with high weight-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether polymorphisms across interleukin (IL)-1, IL-2, IL-6, and brain-derived neurotrophic factor (BDNF) genes are associated with antipsychotic-induced weight gain (AIWG).Methods: Nineteen polymorphisms were genotyped using Taqman® assays in 188 schizophrenia patients on antipsychotic treatment for up to 14 weeks. Mean weight change (%) from baseline was compared across genotypic groups using ANCOVA. A replication sample was used to validate findings.Results: In Europeans, IL-1 rs16944*GA (p=0.013), IL-1 rs1143634*G (p=0.001), and BDNF Val66Met (Val/Val, p=0.004) were associated with greater AIWG, as were IL-1 rs4849127*A (p=0.049), and IL-1 rs16944*GA (p=0.012) in African Americans. Epistatic effects were observed between BDNF Val66Met and IL-1 rs13032029 (Val/Met+TT, PM.Sc