Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families.
Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.
Department of Neuropsychiatry, Nihon University, School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, Japan 173-8610.
Shun-Ying
SY
Yu
Sakae
S
Takahashi
Tadao
T
Arinami
Tatsunobu
T
Ohkubo
Yasundo
Y
Nemoto
Eiichi
E
Tanabe
Yoichi
Y
Fukura
Masato
M
Matsuura
Yong-Hua
YH
Han
Ru-Len
RL
Zhou
Yu-Cun
YC
Shen
Eisuke
E
Matsushima
Takuya
T
Kojima
D000483:Alleles; D004252:DNA Mutational Analysis; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009711:Nucleotides / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D011116:Polynucleotide 5'-Hydroxyl-Kinase / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D009711:Nucleotides; D011943:Receptors, Adrenergic, beta; D011116:Polynucleotide 5'-Hydroxyl-Kinase; D019204:GTP-Binding Proteins