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Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

ABSTRACT: Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complications. Two loci, chr19p13.11 and chr4q12, are genome-wide significant (p?-8) in both association scans and are replicated in an independent cohort. The genes implicated at these two loci are GDF15 and IGFBP7 respectively, both known to be involved in placentation, appetite, and cachexia. While proving the casual roles of GDF15 and IGFBP7 in nausea and vomiting of pregnancy requires further study, this GWAS provides insights into the genetic risk factors contributing to the disease.

SUBMITTER: Fejzo MS

PROVIDER: S-EPMC5862842 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

Fejzo Marlena S MS Sazonova Olga V OV Sathirapongsasuti J Fah JF Hallgrímsdóttir Ingileif B IB Vacic Vladimir V MacGibbon Kimber W KW Schoenberg Frederic P FP Mancuso Nicholas N Slamon Dennis J DJ Mullin Patrick M PM

Nature communications 20180321 1

Hyperemesis gravidarum (HG), severe nausea and vomiting of pregnancy, occurs in 0.3-2% of pregnancies and is associated with maternal and fetal morbidity. The cause of HG remains unknown, but familial aggregation and results of twin studies suggest that understanding the genetic contribution is essential for comprehending the disease etiology. Here, we conduct a genome-wide association study (GWAS) for binary (HG) and ordinal (severity of nausea and vomiting) phenotypes of pregnancy complication ...[more]

PMID: 29563502

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Project description:IntroductionThe pathogenesis and risk factors for hyperemesis gravidarum, excessive nausea and vomiting of pregnancy, are not adequately recognized. In our previous study, we found that women with a personal history of nausea in different situations and a family history of nausea and vomiting of pregnancy (NVP) were more likely to have severe NVP. The present study focuses on these themes in association with hyperemesis gravidarum in a hospital setting.Material and methodsWomen with hyperemesis gravidarum (n = 102) were recruited from among patients hospitalized due to hyperemesis gravidarum in Turku University Hospital, Finland. Our control group (Non-NVP group, n = 138) consisted of pregnant women with no NVP. Personal history of nausea in different situations was inquired about in relation to "motion sickness", "seasickness", "migraine", "other kind of headache", "after anesthesia", "during the use of contraception", and "other kinds of nausea". Relatives with NVP were divided into first-degree (mother and sisters) and second-degree (more distant) relatives.ResultsIn univariate analysis, a personal history of motion sickness, seasickness, nausea related to migraine, nausea with other headache and nausea in other situations were associated with hyperemesis gravidarum. After adjusting for age, parity, pre-pregnancy body mass index, marital status, and smoking, motion sickness (adjusted odds ratio [aOR] 5.24, 95% confidence interval [CI] 2.67-10.31, p < 0.0001), seasickness (aOR 4.82, 95% CI 2.32-10.03, p < 0.0001), nausea related to migraine (aOR 3.00, 95% CI 1.58-5.70, p < 0.001), and nausea in other situations (aOR 2.65, 95% CI 1.13-6.20, p = 0.025) remained significant. In multivariable analysis with all history of nausea variables, motion sickness (OR 2.76, 95% CI 1.29-5.89, p = 0.009) and nausea related to migraine (OR 3.10, 95% CI 1.40-6.86, p = 0.005) were associated with hyperemesis gravidarum. Having any affected relative (OR 3.51, 95%CI 1.84-6.73, p = 0.0002), especially a first-degree relative (OR 3.06, 95% CI 1.62-5.79, p = 0.0006), was also associated with hyperemesis gravidarum. Adjustment did not change the results.ConclusionsWomen with a personal history of nausea or a family history of NVP are more likely to suffer from hyperemesis gravidarum. These results are beneficial to better identify and help women at risk for hyperemesis gravidarum.

Project description:BackgroundNausea and vomiting occur 50-90% during the first trimester of pregnancy. However, patients with hyperemesis gravidarum (HG) may be hospitalized at an incidence rate of 0.8-2% before the 20th week of gestational age. The symptoms generally start during the 5-6th gestational weeks, reaching the highest degree during the 9th week, and decline after the 16-20th weeks of gestation. Clinical findings are proportional to the severity of the disease and severe HG is characterized with dehydration, electrolyte imbalance, and nutritional deficiency as a result of vomiting.MethodsThe study population consisted of two groups of pregnant volunteers at 5-12 weeks of gestation: a severe HG group and a control group. The HG severity was scored using the Pregnancy-Unique Quantification of Emesis (and nausea) (PUQE).The serum levels of the maternal Ca, parathyroid hormone (PTH), Na, K, blood urea nitrogen(BUN), creatinine, vitamin D(25OHD3), and the maternal urine NTx levels were compared between the groups.ResultsIn total, 40 volunteers were enrolled in this study: 20 healthy pregnant volunteers and 20 with severe HG. There were no statistically significant differences between the maternal characteristics. The first trimester weight loss of ≥5 kg was significantly higher in the severe HG group (p < 0.001), while the control group had a significantly higher sunlight exposure ratio than the severe HG group (p = 0.021). The urine NTx levels were significantly higher in the severe HG group (39.22 ± 11.68NTx/Cre) than in the control group(32.89 ± 8.33NTx/Cre) (p = 0.028).The serum Ca, PTH, Na, K, BUN, and creatinine levels were similar between the groups (p = 0.738, p = 0.886, p = 0.841, p = 0.957, p = 0.892, and p = 0.824, respectively). In the severe HG group, the serum 25OHD3 levels were significantly lower than in the control group (p < 0.001).ConclusionsThe data from this study indicated that severe HG is associated with increased urine NTx levels. However, large-scale studies are required to understand the clinical significance of this finding, as well as the long-term consequences of elevated urine NTx levels and the underlying mechanisms.Trial registrationNCT02862496 Date of registration: 21/07/2016.

Project description:Introduction There is limited research on effective treatment of Hyperemesis Gravidarum (HG), the most extreme version of nausea and vomiting during pregnancy (NVP). This paper examines current patterns of use and self-reported effectiveness of cannabis/cannabis-based products (CBP) to treat HG. Materials/Methods The study employed a 21-question survey to gather information on demographics, antiemetic prescription use, and experience with cannabis/CBPs among individuals who experienced extreme nausea and vomiting or HG during their pregnancy. Age-adjusted unconditional logistic regression was used to compare odds of symptom relief and weight gain between respondents who used prescription antiemetics and those who used cannabis. Results Of the 550 survey respondents, 84% experienced weight loss during pregnancy; 96% reported using prescription antiemetics and 14% reported cannabis use for HG. Most respondents reported using cannabis/CBPs (71%) because their prescribed antiemetics were self-reported to be ineffective. More than half of cannabis/CBP users reported using products daily or multiple times per day (53%), primarily via smoke inhalation (59%), and mainly either delta-9-tetrahydrocannabinol (THC) only or THC dominant preparations (57%). Eighty-two percent of cannabis/CBP users reported symptom relief, compared to 60% of prescription antiemetic users. Among patients who reported weight loss during pregnancy, 56% of cannabis users reported gaining weight within two weeks of treatment, compared to 25% of prescription antiemetic users. Conclusions Respondents reported using cannabis primarily because prescribed medications were self-reported to be ineffective. Although the survey approach has inherent limitations so results should be interpreted with caution, in this sample, cannabis was self-reported to be more effective than prescription medications in alleviating HG symptoms and enabling pregnancy weight gain. Therefore, depending on the safety profiles, randomized, double-blinded, placebo-controlled trials of cannabis compared to other antiemetics are warranted to determine whether cannabinoids may provide an effective alternative treatment for HG.

Dataset Information

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

Publications

Placenta and appetite genes GDF15 and IGFBP7 are associated with hyperemesis gravidarum.

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