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World J Biol Psychiatry. 2015 Jan;16(1):45-56. doi: 10.3109/15622975.2014.984631.

The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain.

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Pharmacogenetics Research Clinic, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health & Department of Psychiatry, University of Toronto , Toronto, ON , Canada.



Antipsychotics with high weight gain-inducing propensities influence the expression of immune and neurotrophin genes, which have been independently related to obesity indices. Thus, we investigated whether variants in the genes encoding interleukin (IL)-1β, IL-2, and IL-6 and brain-derived neurotrophic factor (BDNF) Val66Met are associated with antipsychotic-induced weight gain (AIWG).


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 analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction.


In European patients, IL-1β rs16944*GA (P = 0.013, Pcorrected = 0.182), IL-1β rs1143634*G (P = 0.001, Pcorrected = 0.014), and BDNF Val66Met (Val/Val, P = 0.004, Pcorrected = 0.056) were associated with greater AIWG, as were IL-1β rs4849127*A (P = 0.049, Pcorrected = 0.784), and IL-1β rs16944*GA (P = 0.012, Pcorrected = 0.192) in African Americans. BDNF Val66Met interacted with both IL-1β rs13032029 (Val/Met+ TT, PPerm = 0.029), and IL-6 rs2069837 (Val/Val+ AA, PPerm = 0.021) in Europeans, in addition to IL-1β rs16944 (Val/Val+ GA, PPerm = 0.006) in African Americans.


SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.


BDNF; IL-1 β; antipsychotic-induced weight gain; cytokine; genetics

[Indexed for MEDLINE]

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