Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2)

Fejzo, Marlena Schoenberg, Myhre, Ronny, Colodro-Conde, Lucía, MacGibbon, Kimber W, Sinsheimer, Janet S., Reddy, M. V. Prasad Linga, Pajukanta, Paivi, Nyholt, Dale R., Wright, Margaret J., Martin, Nicholas G., Engel, Stephanie M., Medland, Sarah E., Magnus, Per and Mullin, Patrick M. (2017) Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2). Molecular and Cellular Endocrinology, 439 C: 308-316. doi:10.1016/j.mce.2016.09.017

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Author Fejzo, Marlena Schoenberg
Myhre, Ronny
Colodro-Conde, Lucía
MacGibbon, Kimber W
Sinsheimer, Janet S.
Reddy, M. V. Prasad Linga
Pajukanta, Paivi
Nyholt, Dale R.
Wright, Margaret J.
Martin, Nicholas G.
Engel, Stephanie M.
Medland, Sarah E.
Magnus, Per
Mullin, Patrick M.
Title Genetic analysis of hyperemesis gravidarum reveals association with intracellular calcium release channel (RYR2)
Journal name Molecular and Cellular Endocrinology   Check publisher's open access policy
ISSN 1872-8057
0303-7207
Publication date 2017-01-05
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.mce.2016.09.017
Open Access Status File (Author Post-print)
Volume 439
Issue C
Start page 308
End page 316
Total pages 9
Place of publication E Park, Shannon, Clare Ireland
Publisher Elsevier Ireland
Language eng
Subject 1303 Biochemistry
1312 Molecular Biology
1310 Endocrinology
Abstract 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.
Formatted abstract
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.
Keyword Hyperemesis gravidarum
Nausea
Pregnancy
RYR2
Vomiting
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID UL1TR000124
GM053275
R01HD058008
N01-ES-75558
1 UO1 NS 047537-01
A79600334
241944
19151/PD/13
APP1103623
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
 
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