DTNBP1 (dystrobrevin binding protein 1) and schizophrenia: Association evidence in the 3 ' end of the gene

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. Copyright (c) 2007 S. Karger AG, Basel