Association between chromogranin b gene polymorphisms and schizophrenia in the Japanese population.
BACKGROUND
We found in previous work a significant association between schizophrenia and D20S95 on chromosome 20p12.3. In this study, we analyzed 10 microsatellite markers and found an association of schizophrenia with D20S882 and D20S905 that flank D20S95. The chromogranin B gene (CHGB) is 30 kb from D20S905. The chromogranin B (secretogranin I) belongs to a series of acidic secretory proteins that are widely expressed in endocrine and neuronal cells, and its cerebrospinal fluid levels have been reported to decrease in patients with chronic schizophrenia.


METHODS
We screened for polymorphisms in CHGB with polymerase chain reaction direct sequencing methods in 24 Japanese schizophrenic patients and identified a total of 22 polymorphisms. Allelic and genotypic distributions of detected polymorphisms were compared between unrelated Japanese schizophrenic patients (n = 192) and healthy control subjects (n = 192).


RESULTS
Statistically significant differences in the allelic distributions were found between schizophrenic patients and control subjects for 1058C/G (A353G) (corrected p = 7.7 x 10(-5)) and 1104A/G (E368E) (corrected p = 8.1 x 10(-6)). The 1058C/G and 1104A/G alleles were in almost complete linkage disequilibrium and were in linkage disequilibrium with D20S95.


CONCLUSIONS
Results suggest that the CHGB variations are involved in the susceptibility to schizophrenia in our study population.
Iijima
Yoshimi
Y
National Institute of Mental Health (YI), National Center of Neurology and Psychiatry, Ichikawa, Chiba, Japan.
Inada
Toshiya
T
Ohtsuki
Tsuyuka
T
Senoo
Hisashi
H
Nakatani
Masaki
M
Arinami
Tadao
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D053378:Chromogranin B; D002864:Chromogranins / Q000235:genetics*; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D016384:Consensus Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D018895:Microsatellite Repeats; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D051381:Rats; D012016:Reference Values; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D017384:Sequence Deletion
C506134:CHGB protein, human; D053378:Chromogranin B; D002864:Chromogranins; C506137:chromogranin B, mouse; C506140:chromogranin B, rat