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| PMID |
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| TITLE |
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| Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2). |
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| ABSTRACT |
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| 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 Elsevier Ireland Ltd. All rights reserved. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2016/07/09 |
| revised |
2016/08/19 |
| accepted |
2016/09/19 |
| pubmed |
2016/09/25 06:00 |
| medline |
2017/11/29 06:00 |
| entrez |
2016/09/25 06:00 |
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| AUTHORS |
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| 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 |
Lucía |
L |
|
Psychiatric Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
| MacGibbon KW |
|
MacGibbon |
Kimber W |
KW |
|
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 MVPL |
|
Reddy |
M V Prasad Linga |
MVPL |
|
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. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 439 |
| ISSUE: |
| TITLE: Molecular and cellular endocrinology |
| ISOABBREVIATION: Mol Cell Endocrinol |
| YEAR: 2017 |
| MONTH: 01 |
| DAY: 05 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1872-8057 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mol Cell Endocrinol |
| COUNTRY: Ireland |
| ISSNLINKING: 0303-7207 |
| NLMUNIQUEID: 7500844 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
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| COMMENTS AND CORRECTIONS |
|
|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| KL2 TR000122 |
NCATS NIH HHS |
United States |
| R01 HD058008 |
NICHD NIH HHS |
United States |
| R01 GM053275 |
NIGMS NIH HHS |
United States |
| UL1 TR001881 |
NCATS NIH HHS |
United States |
| U01 NS047537 |
NINDS NIH HHS |
United States |
| UL1 TR000124 |
NCATS NIH HHS |
United States |
| KL2 RR033185 |
NCRR NIH HHS |
United States |
| N01ES75558 |
NIEHS NIH HHS |
United States |
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| GENERAL NOTE |
|
|
| KEYWORDS |
|
| KEYWORD |
| Hyperemesis gravidarum |
| Nausea |
| Pregnancy |
| RYR2 |
| Vomiting |
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| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Australia |
|
| Calcium |
metabolism |
| Cohort Studies |
metabolism |
| Exome |
genetics |
| Family |
genetics |
| Female |
genetics |
| Gene Deletion |
genetics |
| Gene Dosage |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genome-Wide Association Study |
genetics |
| Humans |
genetics |
| Hyperemesis Gravidarum |
genetics |
| Intracellular Space |
metabolism |
| Male |
metabolism |
| Norway |
metabolism |
| Parenteral Nutrition |
metabolism |
| Pedigree |
metabolism |
| Pregnancy |
metabolism |
| Ryanodine Receptor Calcium Release Channel |
genetics |
| Sequence Analysis, DNA |
genetics |
| United States |
genetics |
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| SUPPLEMENTARY MESH |
|
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| GENE SYMBOLS |
|
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| CHEMICALS |
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| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Ryanodine Receptor Calcium Release Channel |
| SY7Q814VUP |
Calcium |
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| OTHER ID's |
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