Association of AKT1 gene polymorphisms with risk of schizophrenia and with response to antipsychotics in the Chinese population.
BACKGROUND
A number of studies have pointed to the involvement of AKT signaling pathways in the etiology of schizophrenia. The purpose of this study was to determine whether the AKT1 gene is involved in the etiology of schizophrenia and whether it affects therapeutic outcomes in the Chinese population.


METHODS
Five single nucleotide polymorphisms (SNPs) were genotyped among 384 schizophrenic patients (DSM-IV criteria) and 384 healthy controls from the Chinese population. We systematically analyzed the association of the AKT1 gene with schizophrenia on the basis of sex, age at onset, therapeutic response to typical antipsychotics and atypical antipsychotics, and presence or absence of extrapyramidal syndrome. The study was conducted from May 2004 to June 2006.


RESULTS
We found a positive association of the G allele of the SNP marker rs3803300 with schizophrenia (p = .003), both in early-onset and late-onset subjects, and that a haplotype A-G-C-G-A constructed by the 5 SNPs showed significant association (p = .00004886). However, we found no relationship between any of the 5 SNP markers and therapeutic response to typical and atypical antipsychotics and chlorpromazine-induced extrapyramidal syndrome.


CONCLUSIONS
Our study suggests that AKT1 is a susceptibility gene for schizophrenia in the Chinese population and that the AKT1 gene may play no major role in the therapeutic response to antipsychotics or in chlorpromazine-induced extrapyramidal syndrome.
Xu
Ming-Qing
MQ
Bio-X Center, Shanghai Jiao Tong University, PR China.
Xing
Qing-He
QH
Zheng
Yong-Lan
YL
Li
Sheng
S
Gao
Jian-Jun
JJ
He
Guang
G
Guo
Ting-Wei
TW
Feng
Guo-Yin
GY
Xu
Feng
F
He
Lin
L
D000328:Adult; D017668:Age of Onset; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000208:ethnology; D002681:China; D002746:Chlorpromazine / Q000009:adverse effects / Q000627:therapeutic use*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D014150:Antipsychotic Agents; D017931:DNA Primers; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002746:Chlorpromazine