Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27663074
TITLE
Hyperemesis gravidarum associated with RYR2 genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2).
ABSTRACT
NlmCategory: UNASSIGNED
Hyperemesis Gravidarum (HG), severe nausea/vomiting in pregnancy (NVP), can cause poor maternal/fetal outcomes. Genetic predisposition suggests the genetic component is essential in discovering an etiology. We performed whole-exome sequencing of 5 families followed by analysis of variants in 584 cases/431 controls. Variants in RYR2 segregated with disease in 2 families. The novel variant L3277R was not found in any case/control. The rare variant, G1886S was more common in cases (p = 0.046) and extreme cases (p = 0.023). Replication of G1886S using Norwegian/Australian data was supportive. Common variants rs790899 and rs1891246 were significantly associated with HG and weight loss. Copy-number analysis revealed a deletion in a patient. RYR2 encodes an intracellular calcium release channel involved in vomiting, cyclic-vomiting syndrome, and is a thyroid hormone target gene. Additionally, RYR2 is a downstream drug target of Inderal, used to treat HG and CVS. Thus, herein we provide genetic evidence for a pathway and therapy for HG.
Copyright 2016. Published by Elsevier Ireland Ltd.
DATE PUBLISHED
2016 Sep 20
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/07/09
revised 2016/08/19
accepted 2016/09/19
entrez 2016/09/25 06:00
pubmed 2016/09/25 06:00
medline 2016/09/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Fejzo MS Fejzo Marlena Schoenberg MS Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: mfejzo@mednet.ucla.edu.
Myhre R Myhre Ronny R Norwegian Institute of Public Health, Oslo Norway.
Colodro-Conde L Colodro-Conde Lucia L Psychiatric Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Macgibbon K Macgibbon Kimber K Hyperemesis Education and Research Foundation, Damascus, OR, USA.
Sinsheimer JS Sinsheimer Janet S JS Departments of Biostatistics, Biomathematics, & Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Reddy MV Reddy M V Prasad Linga MV Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Pajukanta P Pajukanta Päivi P Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Wright MJ Wright Margaret J MJ Queensland Brain Institute and Centre for Advanced Imaging, University of Queensland, Brisbane, Australia.
Martin NG Martin Nicholas G NG Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Engel SM Engel Stephanie M SM Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Medland SE Medland Sarah E SE Psychiatric Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Magnus P Magnus Per P Norwegian Institute of Public Health, Oslo Norway.
Mullin PM Mullin Patrick M PM Department of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Molecular and cellular endocrinology
ISOABBREVIATION: Mol. Cell. Endocrinol.
YEAR: 2016
MONTH: Sep
DAY: 20
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1872-8057
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Cell Endocrinol
COUNTRY: Ireland
ISSNLINKING: 0303-7207
NLMUNIQUEID: 7500844
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Hyperemesis gravidarum
Nausea
Pregnancy
RYR2
Vomiting
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's