| Abstract |
Chromosome 22q12 is one of the most promising regions for harboring a risk gene forschizophrenia。We have reported significant linkage of intermediate phenotypes forschizophreniawith 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 theADRBK2was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of theADRBK2gene for mutations in 48schizophreniaprobands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations withschizophreniain 113 family trios ofschizophreniaprobands. 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 andschizophrenia。Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms andschizophrenia。目前的研究表明that theADRBK2gene is unlikely to contribute strongly toschizophreniasusceptibility in this set of families. |