Association analysis of adenosine A1 receptor gene (ADORA1) polymorphisms with schizophrenia in a Japanese population.
OBJECTIVE
The human adenosine A1 receptor gene (ADORA1) localizes to chromosome 1q32 is 76.8 kbp in length and contains six exons. ADORA1 is ubiquitously expressed in the central nervous system and clinical and pharmacological evidence suggest the involvement of adenosine neurotransmission in the pathogenesis of schizophrenia. Therefore, we investigated the contribution of genetic variations of ADORA1 to the pathophysiological mechanisms of Japanese schizophrenia patients.


METHODS
We performed genetic analysis of 29 polymorphic markers in 200 schizophrenic patients and 210 healthy controls from the Kyushu region of Japan. In statistical analysis, we performed the univariate analysis with genotypes and allele frequencies, linkage disequilibrium (LD) analyses, multivariate analysis, haplotype analysis, and sliding window haplotype analysis.


RESULTS
In univariate analysis, no statistical difference was shown, after Bonferroni correction. By LD analysis, however, we could not find any LD blocks. In haplotype analysis, a total of 359 haplotypes were estimated. In multivariate analysis, we found three statistically different markers. In sliding window haplotype analysis, there were four statistically different haplotypes.


CONCLUSIONS
This is the first study describing the involvement of ADORA1 polymorphisms in the pathophysiological mechanisms of schizophrenia in a Japanese population. These results corroborate our previous pharmacological and neurochemical studies in the rat that have suggested an association between ADORA1 neurotransmission and the schizophrenic effects of the N-methyl-D-aspartate receptor antagonist phencyclidine. Thus, ADORA1 polymorphisms may represent good candidate markers for schizophrenia research and ADORA1 may be involved in the pathophysiological mechanisms of schizophrenia in Japanese populations.
Gotoh
Leo
L
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-Ku, Japan.
Mitsuyasu
Hiroshi
H
Kobayashi
Yuki
Y
Oribe
Naoya
N
Takata
Atsushi
A
Ninomiya
Hideaki
H
Stanton
Vincent P
VP
Springett
Gregory M
GM
Kawasaki
Hiroaki
H
Kanba
Shigenobu
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
D017931:DNA Primers; D043682:Receptor, Adenosine A1