Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22.
We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2-L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia.
Mimmack
Michael L
ML
Department of Neurobiology, Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Ryan
Margaret
M
Baba
Hajime
H
Navarro-Ruiz
Juani
J
Iritani
Shuji
S
Faull
Richard L M
RL
McKenna
Peter J
PJ
Jones
Peter B
PB
Arai
Heii
H
Starkey
Michael
M
Emson
Piers C
PC
Bahn
Sabine
S
D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics*; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000235:genetics*; D015854:Up-Regulation
C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL