| Literature DB >> 27663074 |
Marlena Schoenberg Fejzo1, Ronny Myhre2, Lucía Colodro-Conde3, Kimber W MacGibbon4, Janet S Sinsheimer5, M V Prasad Linga Reddy6, Päivi Pajukanta6, Dale R Nyholt7, Margaret J Wright8, Nicholas G Martin9, Stephanie M Engel10, Sarah E Medland3, Per Magnus2, Patrick M Mullin11.
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. Copyright ÂEntities:
Keywords: Hyperemesis gravidarum; Nausea; Pregnancy; RYR2; Vomiting
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Year: 2016 PMID： 27663074 PMCID： PMC6464816 DOI： 10.1016/j.mce.2016.09.017
Source DB: PubMed Journal: Mol Cell Endocrinol ISSN： 0303-7207 Impact factor: 4.369