Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in japanese case-control samples and the nimh genetics initiative bipolar pedigrees

Association between serotonin 4 receptor gene polymorphisms and bipolar disorder in japanese case-control samples and the nimh genetics initiative bipolar pedigrees


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ABSTRACT Possible irregularities in serotonergic neurotransmission have been suggested as causes of a variety of neuropsychiatric diseases. We performed mutation and association analyses of


the _HTR4_ gene, on 5q32, encoding the serotonin 4 receptor in mood disorders and schizophrenia. Mutation analysis was performed on the _HTR4_ exons and exon/intron boundaries in 48 Japanese


patients with mood disorders and 48 patients with schizophrenia. Eight polymorphisms and four rare variants were identified. Of these, four polymorphisms at or in close proximity to exon d,


g.83097C/T (_HTR4_-SVR (splice variant region) SNP1), g.83159G/A (_HTR4_-SVRSNP2), g.83164 (T)9–10 (_HTR4_-SVRSNP3), and g.83198A/G (_HTR4_-SVRSNP4), showed significant association with


bipolar disorder with odds ratios of 1.5 to 2. These polymorphisms were in linkage disequilibrium, and only three common haplotypes were observed. One of the haplotypes showed significant


association with bipolar disorder (_P_ = 0.002). The genotypic and haplotypic associations with bipolar disorder were confirmed by transmission disequilibrium test in the NIMH Genetics


Initiative Bipolar Pedigrees with ratios of transmitted to not transmitted alleles of 1.5 to 2.0 (_P_ = 0.01). The same haplotype that showed association with bipolar disorder was suggested


to be associated with schizophrenia in the case-control analysis (_P_ = 0.003) but was not confirmed when Japanese schizophrenia families were tested. The polymorphisms associated with mood


disorder were located within the region that encodes the divergent C-terminal tails of the 5-HT4 receptor. These findings suggest that genomic variations in the _HTR4_ gene may confer


susceptibility to mood disorder. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your


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22 _Am J Med Genet_ 1997 74: 238–246 Article  CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS Data and biomaterials were collected in four projects that participated in the


National Institute of Mental Health (NIMH) Bipolar Disorder Genetics Initiative. From 1991–98, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN,


U01 MH46282, John Nurnberger, MD, PhD, Marvin Miller, MD, and Elizabeth Bowman, MD; Washington University, St Louis, MO, U01 MH46280, Theodore Reich, MD, Allison Goate, PhD, and John Rice,


PhD; Johns Hopkins University, Baltimore, MD U01 MH46274, J Raymond DePaulo, Jr, MD, Sylvia Simpson, MD, MPH, and Colin Stine, PhD; NIMH Intramural Research Program, Clinical Neurogenetics


Branch, Bethesda, MD, Elliot Gershon, MD, Diane Kazuba, BA, and Elizabeth Maxwell, MSW. This study was supported by the grant of Research on Brain Science (H12-Brain-006) and the grant for


Nervous and Mental Disorders from the Ministry of Health, Labor and Welfare, Japan. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medical Genetics, Institute of Basic Medical


Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan T Ohtsuki, H Ishiguro & T Arinami * National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA S D


Detera-Wadleigh * Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Saitama, Japan T Toyota, K Yamada, K Yoshitsugu, E Hattori & T Yoshikawa * Department of


Neuropsychiatry, Hokushin General Hospital, Nagano, Japan H Shimizu Authors * T Ohtsuki View author publications You can also search for this author inPubMed Google Scholar * H Ishiguro View


author publications You can also search for this author inPubMed Google Scholar * S D Detera-Wadleigh View author publications You can also search for this author inPubMed Google Scholar *


T Toyota View author publications You can also search for this author inPubMed Google Scholar * H Shimizu View author publications You can also search for this author inPubMed Google Scholar


* K Yamada View author publications You can also search for this author inPubMed Google Scholar * K Yoshitsugu View author publications You can also search for this author inPubMed Google


Scholar * E Hattori View author publications You can also search for this author inPubMed Google Scholar * T Yoshikawa View author publications You can also search for this author inPubMed 


Google Scholar * T Arinami View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to T Arinami. RIGHTS AND PERMISSIONS


Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ohtsuki, T., Ishiguro, H., Detera-Wadleigh, S. _et al._ Association between serotonin 4 receptor gene polymorphisms and bipolar


disorder in Japanese case-control samples and the NIMH Genetics Initiative Bipolar Pedigrees. _Mol Psychiatry_ 7, 954–961 (2002). https://doi.org/10.1038/sj.mp.4001133 Download citation *


Received: 07 January 2002 * Accepted: 04 March 2002 * Published: 25 October 2002 * Issue Date: 01 October 2002 * DOI: https://doi.org/10.1038/sj.mp.4001133 SHARE THIS ARTICLE Anyone you


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Springer Nature SharedIt content-sharing initiative KEYWORDS * _HTR4_ * schizophrenia * affective disorder * polymorphism * haplotype * transmission disequilibrium test * association