Zakharyan R, Petrek M, Arakelyan A, Mrazek F, Atshemyan S, Boyajyan A
Laboratory of Macromolecular Complexes, Institute of Molecular Biology, National Academy of Sciences of Republic of Armenia, Yerevan, Armenia.
Tissue Antigens. 2012 Aug;80(2):136-42. doi: 10.1111/j.1399-0039.2012.01886.x. Epub 2012 May 10.
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 rs1800795C 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 rs1800795C 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.
精神分裂症是一种伴有炎症成分的严重精神疾病。多项研究表明，精神分裂症患者血液中促炎细胞因子白细胞介素-6（IL-6）水平升高。然而，仅有有限的研究探讨了该细胞因子在精神分裂症中的过量产生与基因变异之间的关系，且结果存在争议。在此，我们研究了白细胞介素-6基因（IL6）rs1800795（-174G/C）多态性与精神分裂症的可能关联，以及该多态性与白细胞介素-6蛋白（IL-6）血液水平之间的关系。其他研究人员发现这种多态性与IL-6的不同转录速率和不同血浆水平相关。通过序列特异性引物聚合酶链反应对总共208名无亲缘关系的亚美尼亚人进行基因分型，并通过酶联免疫吸附测定法评估IL-6水平。两组中IL6 rs1800795等位基因和基因型均处于哈迪-温伯格（H-W）平衡状态。我们发现rs1800795C等位基因[38%对24%，P = 0.002，比值比（OR）= 1.95，95%置信区间（CI）：1.18 - 2.14]及其携带者（62%对42%，P = 0.003，OR = 2.28，95% CI：1.13 - 1.94）在患者中比在对照组中更常见。患者的IL-6水平比对照组高1.5倍（均值±标准差：6.41±2.47 pg/ml对4.15±1.42 pg/ml，P = 1.9E - 19）。在两组中，观察到rs1800795 GG基因型携带者的IL-6水平高于rs1800795C等位基因携带者（GG对GC + CC，患者：7.02±2.83 pg/ml对5.39±1.2 pg/ml，P = 0.0006；对照组：5.21±1.17 pg/ml对3.38±1.03 pg/ml，P = 1.6E - 15）。总之，我们报告了IL6 rs1800795和较高的IL-6水平与精神分裂症相关。我们还得出结论，IL6 rs1800795*C等位基因与IL-6血液水平升高有关，至少在亚美尼亚人群中可能是精神分裂症发病的一个危险因素。
