A resistance gene in disguise for schizophrenia?
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.
Doi
Nagafumi
N
Department of Neuropsychiatry, University of Tokyo, Tokyo, Japan. Nagafumid@aol.com
Itokawa
Masanari
M
Hoshi
Yoko
Y
Arai
Makoto
M
Furukawa
Aizou
A
Ujike
Hiroshi
H
Sora
Ichiro
I
Yoshikawa
Takeo
T
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*
D004272:DNA, Mitochondrial; D009478:Neuropeptide Y