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  • Title: DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3' end of the gene.
    Author: Duan J, Martinez M, Sanders AR, Hou C, Burrell GJ, Krasner AJ, Schwartz DB, Gejman PV.
    Journal: Hum Hered; 2007; 64(2):97-106. PubMed ID: 17476109.
    Abstract:
    OBJECTIVES: Dysbindin (DTNBP1) has been identified as a susceptibility gene for schizophrenia (SZ) through a positional approach. However, a variety of single nucleotide polymorphisms (SNPs) and haplotypes, in different parts of the gene, have been reported to be associated in different samples, and a precise molecular mechanism of disease remains to be defined. We have performed an association study with two well-characterized family samples not previously investigated at the DTNBP1 locus. METHODS: We examined 646 subjects in 136 families with SZ, largely of European ancestry (EA), genotyping 26 SNPs in DTNBP1. RESULTS: Three correlated markers (rs875462, rs760666, and rs7758659) at the 3' region of DTNBP1 showed evidence for association to SZ (p = 0.004), observed in both the EA (p = 0.031) and the African American (AA) subset (p = 0.045) with the same over-transmitted allele. The most significant haplotype in our study was rs7758659-rs3213207 (global p = 0.0015), with rs3213207 being the most frequently reported associated marker in previous studies. A non-conservative missense variant (Pro272Ser) in the 3' region of DTNBP1 that may impair DTNBP1 function was more common in SZ probands (8.2%) than in founders (5%) and in dbSNP (2.1%), but did not reach statistical significance. CONCLUSION: Our results provide evidence for an association of SZ with SNPs at the 3' end of DTNBP1 in the samples studied.
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