title: A resistance gene in disguise for schizophrenia?
abstract: We examined the hypothesis that -485 T, a novel polymorphism in the promoter region of the neuropeptide Y gene which was shown to be associated with schizophrenia in our previous paper, confers susceptibility to the disease. For a case-control association study, 331 unrelated Japanese schizophrenics (S(1): milder cases in the previous study, n = 212; and S(2): additional severer cases, n = 119) and 199 unrelated normal controls were recruited. Contribution of -485 T to the risk and the severity of the illness was examined by (1) comparing the risk in each genotype in the general population, (2) testing correlations between the gene-dose of -485 T, and the severity of chronic outcome in S(2) assessed with the Positive and Negative Symptom Scale, and (3) comparing the distribution of age at onset in S(1) + S(2) among the three genotypes. -485 T was significantly associated with schizophrenia in S(1) + S(2). Significant negative correlations were observed between the gene-dose and the symptom assessment scores in all items. The homozygote of -485 T showed a second peak frequency in the late-onset group both in males and females, while the homozygote of the alternative allele showed a single peak in the early-onset group. The higher risk of schizophrenia in the heterozygote than in the homozygote of -485 T in the general population did not support the possibility of linkage disequilibrium with a susceptibility gene. -485 T most likely confers resistance but not susceptibility to schizophrenia. An interaction between a nuclear resistance gene and a presumptive pathogenic gene in the mitochondrial DNA was suggested.
authors.affiliation: Department of Neuropsychiatry, University of Tokyo, Tokyo, Japan. Nagafumid@aol.com
authors.forename: Nagafumi
authors.initials: N
authors.lastname: Doi
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hoshi
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Aizou
authors.initials: A
authors.lastname: Furukawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sora
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D017677:Age Distribution; D017668:Age of Onset; D000483:Alleles; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009478:Neuropeptide Y / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D009478:Neuropeptide Y