Family-based association study of DTNBP1 in 6p22. 3 and schizophrenia

JX Tang, J Zhou, JB Fan, XW Li, YY Shi, NF Gu… - Molecular …, 2003 - nature.com
JX Tang, J Zhou, JB Fan, XW Li, YY Shi, NF Gu, GY Feng, YL Xing, JG Shi, L He
Molecular Psychiatry, 2003nature.com
SIR–The existence of an important genetic contribution to the etiology of schizophrenia is
well established from genetic epidemiological studies. Recently, a study performed by
Straub et al1 showed that the gene of DTNBP1 (dystrobrevin-binding protein 1) located on
6p22. 3, a high-susceptibility chromosome region of schizophrenia, was highly associated
with schizophrenia in Irish high-density pedigrees. DTNBP1, the human ortholog of mouse
dysbindin, appears to have a role in neuromuscular synapse formation and maintenance. 2 …
SIR–The existence of an important genetic contribution to the etiology of schizophrenia is well established from genetic epidemiological studies. Recently, a study performed by Straub et al1 showed that the gene of DTNBP1 (dystrobrevin-binding protein 1) located on 6p22. 3, a high-susceptibility chromosome region of schizophrenia, was highly associated with schizophrenia in Irish high-density pedigrees. DTNBP1, the human ortholog of mouse dysbindin, appears to have a role in neuromuscular synapse formation and maintenance. 2 It is found in multiple locations within the central nervous system, so it may also have a possible function in signal transduction. 2, 3 In the present study, to confirm and extend Straub’s findings of DTNBP1 in independent samples, we investigated seven SNPs within 140-kb length of the gene DTNBP1 in 233 Han Chinese trios.
Parent–offspring trios used in this study containing 173 trios from Shanghai and 60 from Xi’an (131 male and 102 female probands with a mean age of 22.88, SD ¼ 0.57) were also involved in our previous study. 4 The unrelated schizophrenic probands were collected from Shanghai Mental Health Center and Xi’an Mental Health Center, respectively. Clinical diagnosis was made according to DSM-IIIR criteria5 by two independent clinicians. A standard informed consent, which was reviewed and approved by the Shanghai Ethnical Committee of Human Genetic Resources, was given by the participated subjects after the nature of study had been fully explained. All subjects were Han Chinese in origin. Seven SNPs (P1328, P1287, P1655, P1635, P1763, P1578 and P1583) adopted in Straub’s work were genotyped in all our trios samples. The genotyping assay combines kinetic (real-time quantitative) PCR with allele-specific amplification, which was described elsewhere. 6 Kinetic PCR reactions were performed on an ABI PRISM 7900 Sequence Detection System (Applied Biosystems).
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