TY - JOUR
T1 - The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain
AU - Fonseka, Trehani M.
AU - Tiwari, Arun K.
AU - Gonc¸alves, Vanessa F.
AU - Lieberman, Jefrey A.
AU - Meltzer, Herbert Y.
AU - Goldstein, Benjamin I.
AU - Kennedy, James L.
AU - Kennedy, Sidney H.
AU - Müller, Daniel J.
N1 - Funding Information:
The authors would like to thank the participants of this study. we have no acknowledgements of assistance to disclose. TMF is a recipient of a Canadian institutes of health research (Cihr) 2012 Frederick banting and Charles best Masters award. akT is a recipient of a narsad 2010 young investigator award. Jlk is a recipient of a Cihr operating grant. shk has received grant/research support from: lundbeck, ontario brain institute, Cihr, st. Jude Medical, bristol-Myers squibb and Clera inc. dJM has received the following: Cihr operating grant (Genetics of antipsychotics induced Metabolic syndrome, MoP 89853), brain & behaviour research Foundation narsad independent investigator award, Cihr Michael smith new investigator salary Prize for research in schizophrenia, early researcher award from the ontario Ministry of research and innovation, and a new investigator Fellowship from the ontario Mental health Foundation (oMhF). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of these organizations.
Publisher Copyright:
© 2015 Informa Healthcare.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Objectives. 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). 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 analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. Results. 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. Conclusions. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.
AB - Objectives. 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). 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 analysis of covariance (ANCOVA). Epistatic effects between cytokine polymorphisms and BDNF Val66Met were tested using Model-Based Multifactor Dimensionality Reduction. Results. 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. Conclusions. SNPs across IL-1β and BDNF Val66Met may influence AIWG. Replication of these findings in larger, independent samples is warranted.
KW - Antipsychotic-induced weight gain
KW - Cytokine
KW - Genetics
KW - IL-1β, BDNF
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UR - http://www.scopus.com/inward/citedby.url?scp=84920854814&partnerID=8YFLogxK
U2 - 10.3109/15622975.2014.984631
DO - 10.3109/15622975.2014.984631
M3 - Article
C2 - 25521684
AN - SCOPUS:84920854814
SN - 1562-2975
VL - 16
SP - 45
EP - 56
JO - World Journal of Biological Psychiatry
JF - World Journal of Biological Psychiatry
IS - 1
ER -
