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Polymorphic Lengths of Dinucleotide $(GT)^n$ Repeats in Upstream of Human nNOS Exon 1f Gene Play a Role in Modulating the nNOS Transcription: Clinical Implications  

Shin, Mi-Kyung (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
Kim, Kyung-Nam (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
Kim, Chul-Eung (Department of Psychiatry, Inha University Hospital, College of Medicine, Inha University)
Lee, Sung-Keun (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
Kang, Ju-Hee (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
Park, Chang-Shin (Department of Pharmacology, Center for Advanced Medical Education, Inha University College of Medicine by BK-21 Project)
Publication Information
Molecular & Cellular Toxicology / v.4, no.1, 2008 , pp. 11-15 More about this Journal
Abstract
The expression of neuronal nitric oxide synthase (nNOS) is regulated by various spliced first exons (exon 1a-1i), sharing differentially common exon 2 in diverse human tissues. The highly complex structure and regulation of human nNOS gene gave limitations of information for the precise mechanism of nNOS regulation. In the present study, we report that the repeats of polymorphic dinucleotides $(GT)^nA(TG)^n$ repeats located in just upstream to the exon 1f in human nNOS gene play suppressive role in transcription, as shown in the characteristics of Z-DNA motif in other genes. In neuronal and trophoblast cells transfected transiently with luciferase construct without dinucleotide repeats at the 5'-flanking region of exon 1f in nNOS gene, the luciferase activity was increased markedly. However, the presence of the dinucleotide repeats dramatically suppressed the luciferase activity to the basal level, and which was dependent on the length of $(GT)^n$ and $(TG)^n$ repeats. More importantly, we found the polymorphisms in the length of dinucleotide repeats in human. Furthermore, we show for the first time here that there is a significant association of the lengths of polymorphic dinucleotide $(GT)^n$ and $(TG)^n$ repeats with the risk of schizophrenia.
Keywords
Neuronal NOS; Dinucleotide repeat; Schizophrenia;
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