Abstract
BackgroundPreeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders.MethodsIt was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP.ResultsThe genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04–2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity.ConclusionsThe HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.
Highlights
Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined
We aimed to investigate whether gestational hypertensive disorders are associated with the Histidine-rich glycoprotein (HRG) C633T single nucleotide polymorphisms (SNP) in women pregnant with singletons without previous comorbidities associated with hypertension
Genetic distribution among cases and controls Regarding the genotype distribution of the HRG C633T SNP in the population, the homozygous C/C genotype was more prevalent among controls compared to cases (Table 1)
Summary
Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders. Preeclampsia is estimated to affect 2–8% of pregnancies globally and accounts for 10–15% of maternal mortality, as well as for 25% of periand neo-natal mortality worldwide [2] It is nowadays becoming a widely accepted hypothesis that dysregulation of placental vasculature underlies an Elenis et al BMC Medical Genetics (2018) 19:44 leading to the clinical manifestation of preeclampsia. Its exact role still remains obscure but it has been shown to be involved in the immune system, in coagulation, as well as in angiogenesis and in fertility regulation Supporting the latter biologic function, is the abundance of HRG throughout the female reproductive tract (i.e. in follicular fluid, endometrium, fallopian tube and in myometrium) where the oocyte develops, is fertilized and later implants [9]. The association remained significant even after adjustment for maternal age, maternal BMI and parity (Table 3)
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