TY - JOUR
T1 - Meta-analysis of cytokine and chemokine genes in schizophrenia
AU - Hudson, Zachary D.
AU - Miller, Brian J.
N1 - Funding Information:
Dr. Hudson has nothing to disclose. Dr. Miller has nothing to disclose for the work under consideration. In the past 12 months, Dr. Miller reports employment at Georgia Regents University, grant support from the National Institute of Mental Health (K23MH098014), the American Psychiatric Association (Kempf Fund Award) and Georgia Regents University; Research support from the National Institutes of Health Clinical Loan Repayment Program; Honoraria from Psychiatric Times; and Speaker fees for lectures from the University of Nevada-Reno.
Publisher Copyright:
© 2018 Walsh Medical Media LLC. All rights reserved.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Introduction: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We performed a meta-analysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews. Methods: We identified articles by systematic searches of PubMed, PsycInfo, and ISI, and the reference lists of identified studies. For each cytokine or chemokine polymorphism, we performed an allele- and genotype-wise meta-analysis, using a random effects model. Results: Twenty-one independent studies met the inclusion criteria, comprising polymorphisms for the IL1B, IL2, IL4, IL6, sIL6R, MCP1, and TGFB1 genes. For IL6, the A allele (OR=0.95, 95% CI 0.91-0.99) and AA genotype (OR=0.65, 95% CI 0.50-0.85) for the rs1800795 polymorphism, and for sIL6R, the A allele (OR=0.96 95%, CI 0.92-1.00) and AA genotype (OR=0.72, 95% CI 0.55-0.94) the rs8192284 polymorphism were associated with significantly decreased schizophrenia risk. In the genotype-wise analysis for IL1B, homozygosity for either allele (AA: OR=1.91, 95% CI 1.60-2.27; and GG: OR=0.40, 95% CI 0.33-0.49) of the rs1143627 polymorphism was also significantly associated with schizophrenia risk. Conclusions: Associations between polymorphisms for the IL1B, IL6, and sIL6R genes and schizophrenia risk complement and extend previous findings regarding immune dysfunction in this disorder, including genome-wide association studies. Future studies of cytokine expression in schizophrenia should consider the effect of these polymorphisms. The finding of potential "protective" alleles may also be relevant for at-risk populations.
AB - Introduction: Immune system genes, including cytokines, are associated with schizophrenia risk. Polymorphisms in cytokine genes may also impact on blood levels of cytokines, which are altered in patients with schizophrenia. We performed a meta-analysis of case-control studies of cytokine and chemokine genes in schizophrenia that have not been considered in previous quantitative reviews. Methods: We identified articles by systematic searches of PubMed, PsycInfo, and ISI, and the reference lists of identified studies. For each cytokine or chemokine polymorphism, we performed an allele- and genotype-wise meta-analysis, using a random effects model. Results: Twenty-one independent studies met the inclusion criteria, comprising polymorphisms for the IL1B, IL2, IL4, IL6, sIL6R, MCP1, and TGFB1 genes. For IL6, the A allele (OR=0.95, 95% CI 0.91-0.99) and AA genotype (OR=0.65, 95% CI 0.50-0.85) for the rs1800795 polymorphism, and for sIL6R, the A allele (OR=0.96 95%, CI 0.92-1.00) and AA genotype (OR=0.72, 95% CI 0.55-0.94) the rs8192284 polymorphism were associated with significantly decreased schizophrenia risk. In the genotype-wise analysis for IL1B, homozygosity for either allele (AA: OR=1.91, 95% CI 1.60-2.27; and GG: OR=0.40, 95% CI 0.33-0.49) of the rs1143627 polymorphism was also significantly associated with schizophrenia risk. Conclusions: Associations between polymorphisms for the IL1B, IL6, and sIL6R genes and schizophrenia risk complement and extend previous findings regarding immune dysfunction in this disorder, including genome-wide association studies. Future studies of cytokine expression in schizophrenia should consider the effect of these polymorphisms. The finding of potential "protective" alleles may also be relevant for at-risk populations.
KW - Cytokines
KW - Genetics
KW - Meta-analysis
KW - Schizophrenia
KW - Single nucleotide polymorphisms
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U2 - 10.3371/CSRP.HUMI.070516
DO - 10.3371/CSRP.HUMI.070516
M3 - Article
C2 - 27454212
AN - SCOPUS:85018501530
SN - 1935-1232
VL - 12
SP - 121
EP - 129
JO - Clinical Schizophrenia and Related Psychoses
JF - Clinical Schizophrenia and Related Psychoses
IS - 3
ER -