title: Interleukin-6 promoter polymorphism and plasma levels in patients with schizophrenia.
abstract: Schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin-6 cytokine in schizophrenia. However, only limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin-6 gene (IL6) rs1800795 (-174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin-6 protein (IL-6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL-6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence-specific primers, and IL-6 levels were assessed by enzyme-linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy-Weinberg (H-W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18-2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13-1.94) were more frequent in patients than in controls. IL-6 in patients was 1.5-fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E-19). In both groups, higher IL-6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E-15). In conclusion, we report an association of IL6 rs1800795 and higher IL-6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL-6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population.
authors.affiliation: Laboratory of Macromolecular Complexes, Institute of Molecular Biology, National Academy of Sciences of Republic of Armenia, Yerevan, Armenia.
authors.forename: R
authors.initials: R
authors.lastname: Zakharyan
authors.forename: M
authors.initials: M
authors.lastname: Petrek
authors.forename: A
authors.initials: A
authors.lastname: Arakelyan
authors.forename: F
authors.initials: F
authors.lastname: Mrazek
authors.forename: S
authors.initials: S
authors.lastname: Atshemyan
authors.forename: A
authors.initials: A
authors.lastname: Boyajyan
mesh_terms: D000328:Adult; D000483:Alleles; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D015850:Interleukin-6