Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism
Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism
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DOI：
10.1007/s00702-010-0418-3
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发表时间：
2010-07-01
影响因子：
3.3
通讯作者：
Nawa, H.
中科院分区：
文献类型：
--
作者：
Shibuya, M.;Komi, E.;Nawa, H.
神经调节蛋白-1（NRG 1）基因与精神分裂症的病因学或神经病理学有关，但其生物学作用尚不完全清楚。我们已经建立了一种酶联免疫吸附试验（ELISA），识别NRG 1 β 1免疫球蛋白样（IG）结构域，并测量可溶性Ig-NRG 1免疫反应性的慢性精神分裂症患者（n = 40）和健康志愿者（n = 59）的血清中。ELISA在人血清中检测到显著高浓度的Ig-NRG 1免疫反应性（平均5.97 +/-A0.40 ng/mL，类似于213 +/-A14 pM）。性别和诊断对血清Ig-NRG 1免疫反应性有显著影响。精神分裂症组的平均Ig-NRG 1免疫反应性为对照组的63.2%。女性Ig-NRG 1阳性率为男性的147.1%。我们还尝试将NRG 1基因组的6个SNP与血清Ig-NRG 1免疫反应性相关联。协方差分析与性别补偿确定了诊断和SNP 8 NRG 243177等位基因之间的显着相互作用。该SNP的T等位基因显著导致Ig-NRG 1免疫反应性的疾病相关性降低。虽然我们假设抗精神病药物的慢性影响，但长期氟哌啶醇治疗对猴血清Ig-NRG 1免疫反应性无显著影响。这些结果表明，慢性精神分裂症患者血清NRG 1水平降低，并受到SNP 8 NRG 243177等位基因的影响。
Neuregulin-1 (NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood. We have established an enzyme-linked immunosorbent assay (ELISA), which recognizes the NRG1 beta 1 immunoglobulin-like (Ig) domain, and measured soluble Ig-NRG1 immunoreactivity in the sera of chronic schizophrenia patients (n = 40) and healthy volunteers (n = 59). ELISA detected remarkably high concentrations of Ig-NRG1 immunoreactivity in human serum (mean 5.97 +/- A 0.40 ng/mL, similar to 213 +/- A 14 pM). Gender and diagnosis exhibited significant effects on serum Ig-NRG1 immunoreactivity. Mean Ig-NRG1 immunoreactivity in the schizophrenia group was 63.2% of that measured in the control group. Ig-NRG1 immunoreactivity in women was 147.1% of that seen in men. We also attempted to correlate six SNPs of NRG1 genome with serum Ig-NRG1 immunoreactivity. Analysis of covariance with compensation for gender identified a significant interaction between diagnosis and SNP8NRG243177 allele. The T allele of this SNP significantly contributed to the disease-associated decrease in Ig-NRG1 immunoreactivity. Although we hypothesized a chronic influence of antipsychotic medications, there was no significant effect of chronic haloperidol treatment on serum Ig-NRG1 immunoreactivity in monkeys. These findings suggest that serum NRG1 levels are decreased in patients with chronic schizophrenia and influenced by their SNP8NRG243177 alleles.