Vitamin D receptor polymorphisms and risk of hyperemesis gravidarum

Abstract

OBJECTIVE: Hyperemesis gravidarum (HG), or severe nausea and vomiting of pregnancy, is the most common cause of hospitalization in the first half of pregnancy and is second only to preterm labor for pregnancy overall. HG can be associated with serious maternal morbidity such as Wernicke's encephalopathy, fetal growth restriction, and even maternal and fetal death. There is a strong genetic component to HG and its etiology may be related to defects in pregnancy-related hormones or their receptors. The human placenta synthesizes 1,25-dihydroxyvitamin D3 and expresses the vitamin D receptor (VDR) but their physiologic role in pregnancy remains poorly understood. No studies to date have examined the possibility of VDR polymorphisms increasing susceptibility to HG. METHODS: Our study population consisted of cases recruited from the Hyperemesis Education and Research Foundation (www.helpher.org) and controls who were friends of the cases and who have had at least two previous unaffected pregnancies. Participants were asked to complete an online survey and submit a saliva sample for DNA analysis. DNA was extracted per ethanolprecipitation protocol provided by the manufacturer (Oragene) and genotyping of single nucleotide polymorphisms was performed by TaqMan assay. RESULTS: See table 1. None of the studied VDR genotypes was statistically significantly associated with HG. However, rs10735810 may be associated with early onset of HG ( < 5 weeks, P-value = 0.19). DISCUSSION: A larger number of study participants will be necessary to further evaluate the relationship between VDR polymorphisms and HG. Severity, onset and duration should be investigated as potential modifiers.