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Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum

Introduction Hyperemesis gravidarum (HG), a pregnancy complication characterized by severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies. It is associated with both maternal and fetal morbidity. HG is highly heritable and recurs in approximately 80% of women. In a recent genome...

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Autores principales: Fejzo, Marlena S., Arzy, Daria, Tian, Rayna, MacGibbon, Kimber W., Mullin, Patrick M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Georg Thieme Verlag KG 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138473/
https://www.ncbi.nlm.nih.gov/pubmed/30258246
http://dx.doi.org/10.1055/a-0661-0287
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author Fejzo, Marlena S.
Arzy, Daria
Tian, Rayna
MacGibbon, Kimber W.
Mullin, Patrick M.
author_facet Fejzo, Marlena S.
Arzy, Daria
Tian, Rayna
MacGibbon, Kimber W.
Mullin, Patrick M.
author_sort Fejzo, Marlena S.
collection PubMed
description Introduction Hyperemesis gravidarum (HG), a pregnancy complication characterized by severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies. It is associated with both maternal and fetal morbidity. HG is highly heritable and recurs in approximately 80% of women. In a recent genome-wide association study, it was shown that placentation, appetite, and the cachexia gene GDF15 are linked to HG. The purpose of this study was to explore whether GDF15 alleles linked to overexpression of GDF15 protein segregate with the condition in families, and whether the GDF15 risk allele is associated with recurrence of HG. Methods We analyzed GDF15 overexpression alleles for segregation with disease using exome-sequencing data from 5 HG families. We compared the allele frequency of the GDF15 risk allele, rs16982345, in patients who had recurrence of HG with its frequency in those who did not have recurrence. Results Single nucleotide polymorphisms (SNPs) linked to higher levels of GDF15 segregated with disease in HG families. The GDF15 risk allele, rs16982345, was associated with an 8-fold higher risk of recurrence of HG. Conclusion The findings of this study support the hypothesis that GDF15 is involved in the pathogenesis of both familial and recurrent cases of HG. The findings may be applicable when counseling women with a familial history of HG or recurrent HG. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under development. Based on our findings, patients carrying GDF15 variants associated with GDF15 overexpression should be included in future studies of GDF15-GFRAL-based therapeutics. If safe, this approach could reduce maternal and fetal morbidity.
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spelling pubmed-61384732018-09-24 Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum Fejzo, Marlena S. Arzy, Daria Tian, Rayna MacGibbon, Kimber W. Mullin, Patrick M. Geburtshilfe Frauenheilkd Introduction Hyperemesis gravidarum (HG), a pregnancy complication characterized by severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies. It is associated with both maternal and fetal morbidity. HG is highly heritable and recurs in approximately 80% of women. In a recent genome-wide association study, it was shown that placentation, appetite, and the cachexia gene GDF15 are linked to HG. The purpose of this study was to explore whether GDF15 alleles linked to overexpression of GDF15 protein segregate with the condition in families, and whether the GDF15 risk allele is associated with recurrence of HG. Methods We analyzed GDF15 overexpression alleles for segregation with disease using exome-sequencing data from 5 HG families. We compared the allele frequency of the GDF15 risk allele, rs16982345, in patients who had recurrence of HG with its frequency in those who did not have recurrence. Results Single nucleotide polymorphisms (SNPs) linked to higher levels of GDF15 segregated with disease in HG families. The GDF15 risk allele, rs16982345, was associated with an 8-fold higher risk of recurrence of HG. Conclusion The findings of this study support the hypothesis that GDF15 is involved in the pathogenesis of both familial and recurrent cases of HG. The findings may be applicable when counseling women with a familial history of HG or recurrent HG. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under development. Based on our findings, patients carrying GDF15 variants associated with GDF15 overexpression should be included in future studies of GDF15-GFRAL-based therapeutics. If safe, this approach could reduce maternal and fetal morbidity. Georg Thieme Verlag KG 2018-09 2018-09-14 /pmc/articles/PMC6138473/ /pubmed/30258246 http://dx.doi.org/10.1055/a-0661-0287 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited.
spellingShingle Fejzo, Marlena S.
Arzy, Daria
Tian, Rayna
MacGibbon, Kimber W.
Mullin, Patrick M.
Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title_full Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title_fullStr Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title_full_unstemmed Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title_short Evidence GDF15 Plays a Role in Familial and Recurrent Hyperemesis Gravidarum
title_sort evidence gdf15 plays a role in familial and recurrent hyperemesis gravidarum
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6138473/
https://www.ncbi.nlm.nih.gov/pubmed/30258246
http://dx.doi.org/10.1055/a-0661-0287
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