Genetics of hypertension-related sex differences and hypertensive disorders of pregnancy
Creators: name: Nurkkala, Jouko
name: Vaura, Felix
name: Toivonen, Jenni
name: Niiranen, Teemu
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Genetics
subject: FOS: Biological sciences
subject: Neuroscience
subject: Biotechnology
subject: Evolutionary Biology
subject: Mathematical Sciences not elsewhere classified
subject: Mental Health
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: <b>Background:</b> Hypertension and hypertensive disorders of pregnancy (HDP) cause a significant burden of disease on societies and individuals by increasing cardiovascular disease risk. Environmental risk factors alone do not explain the observed sexual dimorphism in lifetime blood pressure (BP) trajectories nor inter-individual variation in HDP risk. <b>Methods:</b> In this short review, we focus on the genetics of hypertension-related sex differences and HDP and discuss the importance of genetics utilization for sex-specific hypertension risk prediction. <b>Results:</b> Population and twin studies estimate that 28–66% of variation in BP levels and HDP is explained by genetic variation, while genomic wide association studies suggest that BP traits and HDP partly share a common genetic background. Moreover, environmental and epigenetic regulation of these genes differ by sex and oestrogen receptors in particular are shown to convey cardio- and vasculoprotective effects through epigenetic regulation of DNA. The majority of known genetic variation in hypertension and HDP is polygenic. Polygenic risk scores for BP display stronger associations with hypertension risk in women than in men and are associated with sex-specific age of hypertension onset. Monogenic forms of hypertension are rare and mostly present equally in both sexes. <b>Conclusion:</b> Despite recent genetic discoveries providing new insights into HDP and sex differences in BP traits, further research is needed to elucidate the underlying biology. Emphasis should be placed on demonstrating the added clinical value of these genetic discoveries, which may eventually facilitate genomics-based personalized treatments for hypertension and HDP. Blood pressure trajectories and age-related prevalence of hypertension differ between men and women.Vasculoprotective qualities of oestrogen, mediated by oestrogen receptors, are lost at menopause.Certain genetic variants linked to hypertension are sex-specific, i.e. only observed in one sex.Hypertension and preeclampsia are polygenic diseases, i.e. several different genes influence the susceptibility for these conditions.Hypertension and hypertensive disorders of pregnancy have a partially shared genetic basis.The combined effect of several genetic variants can be evaluated using polygenic risk scores (PRSs). Individuals, and especially women, with a high blood pressure PRS develop hypertension a decade earlier compared to those with a low PRS.Environmental and lifestyle factors can modify genetic risk by altering gene expression. Sex differences in the association between gene expression and hypertension remain largely unknown. Blood pressure trajectories and age-related prevalence of hypertension differ between men and women. Vasculoprotective qualities of oestrogen, mediated by oestrogen receptors, are lost at menopause. Certain genetic variants linked to hypertension are sex-specific, i.e. only observed in one sex. Hypertension and preeclampsia are polygenic diseases, i.e. several different genes influence the susceptibility for these conditions. Hypertension and hypertensive disorders of pregnancy have a partially shared genetic basis. The combined effect of several genetic variants can be evaluated using polygenic risk scores (PRSs). Individuals, and especially women, with a high blood pressure PRS develop hypertension a decade earlier compared to those with a low PRS. Environmental and lifestyle factors can modify genetic risk by altering gene expression. Sex differences in the association between gene expression and hypertension remain largely unknown. Hypertension (high blood pressure [BP]) and hypertensive disorders of pregnancy (HDP), such as preeclampsia, increase the risk of heart attacks, stroke and heart failure. Lifestyle factors alone do not explain the BP differences between men and women nor HDP risk in women. Approximately half of the variation in BP levels and HDP is explained by genes, and these two conditions have been partly linked to the same genes. Moreover, the regulation of these genes differs by sex. The majority of the known genetic variation in hypertension and HDP is caused by the additive effect of thousands of genes. Genetic risk scores for BP display stronger associations with hypertension risk in women than in men and are associated with sex-specific age of hypertension onset. Forms of hypertension caused by a single gene are rare and mostly present equally in both sexes. In this short review, we focus on the genetics of hypertension-related sex differences and HDP and discuss the importance of genetics utilisation for sex-specific hypertension risk prediction.