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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Authors	Fejzo, Marlena Schoenberg; Myhre, Ronny; Colodro-Conde, Lucia; 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.
Journal	MOLECULAR AND CELLULAR ENDOCRINOLOGY
Pages	308-316
Volume	439
Date	1/01/2017
Grant ID
Funding Body	Hyperemesis Education and Research Foundation (MSF)
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1016/j.mce.2016.09.017
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