Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism.
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 NRG1beta1 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 +/- 0.40 ng/mL, ~213 +/- 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.
Shibuya
M
M
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Niigata, 951-8585, Japan.
Komi
E
E
Wang
R
R
Kato
T
T
Watanabe
Y
Y
Sakai
M
M
Ozaki
M
M
Someya
T
T
Nawa
H
H
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D020890:Neuregulin-1 / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D012737:Sex Factors
D014150:Antipsychotic Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1; D006220:Haloperidol