Association of the HSPG2 gene with neuroleptic-induced tardive dyskinesia.

Tardive dyskinesia (TD) is characterized by repetitive, involuntary, and purposeless movements that develop in patients treated with long-term dopaminergic antagonists, usually antipsychotics. By a genome-wide association screening of TD in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD (non-TD group) and subsequent confirmation in independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we identified association of a single nucleotide polymorphism, rs2445142, (allelic p=2 x 10(-5)) in the HSPG2 (heparan sulfate proteoglycan 2, perlecan) gene with TD. The risk allele was significantly associated with higher expression of HSPG2 in postmortem human prefrontal brain (p<0.

Ab initio GB study of methylation reaction of adenine, cytosine, guanine, and thymine by methanediazonium ion.

Methylation reaction at ten nucleophilic sites in four DNA base molecules by methanediazonium ion (N(2)Me+) was examined by ab initio MO/GB calculation which includes the solvent effect with the continuum model using the generalized Born formula. The stabilization energy of the ion-dipole complex as well as the energy of the transition state are roughly consistent with the experimental fraction of methylation by N -methyl- N -nitrosourea. For the guanine N7 site, which is the principal site of methylation, the stabilization energy is the largest and the energy of the transition state is low.