The R563Q mutation of theβ-subunit of the epithelial sodium channel gene associated with hypertensive disease and related complications in pregnancy

[摘要] ENGLISH ABSTRACT: Introduction: Hypertensive disease is one of the cardinal causes of maternal morbidity and mortality in South Africa. According to the National Confidential Enquiry into Maternal Deaths (NCEMD) report for 2005-2007, the 'big five causes of maternal death have remained the same as in the previous triennium, with hypertensive disease in second place, being the causative factor in 15.7% of cases.1 Women under 20 years of age were at greater risk of dying due to complications of hypertension. In this light, the early identification and treatment of hypertensive disease remains important priorities in improving maternal care. Various serum markers have been studied to identify women at risk of pre-eclampsia, including biological markers and genetic factors.2 It is also well known that chronic hypertension is one of the major predisposing factors to the development pre-eclampsia.2 A continued search for a genetic screening test to assist in early diagnosis could facilitate a reduction of maternal morbidity and mortality.Aims: The aim of this project is to determine the prevalence of the R563Q mutation of the -subunit of the epithelial sodium channel (-ENaC) gene in a cohort of primigravid women with hypertensive disease in pregnancy and to compare pregnancy outcomes in this group of hypertensive patients to those not identified to be carriers of the mutation.Methodology: A retrospectively collected study cohort of patients with early onset pre-eclampsia, obtained from pooled samples and data from the GAP study (Genetic Aspects of Pre-eclampsia, project number C99/025), was used. The planned sample size was 200, with 200 controls who were ethnic-matched, normotensive women. Exclusion criteria were gestation 34 weeks, multiple pregnancy, known underlying collagen vascular disease and type I Diabetes Mellitus. Outcome criteria: The pregnancy outcomes were analysed with respect to the degree of hypertensive disease and related complications (maternal, placental and neonatal). Results: Blood samples form 104 patients and 80 control samples were analysed. Pre-eclamptic patients were significantly younger than controls (p<0.0001). The presence of the mutation was not significantly increased in the pre-eclamptic group (p=0.33). The mutation bearers did not exhibit a significant tendency towards a specific degree of pre-eclampsia (p=0.51). There were no significant differences in the other studied maternal or fetal outcome measures. A composite outcome (the presence of 1 adverse outcome compared to no adverse outcome) was created which did not differ between the mutation positive and negative pre-eclamptic patients. Data of the index study was combined with the data form a prior relevant study9 and combined odds ratios were calculated. The increased mutation frequency amongst pre-eclamptics compared to healthy controls then remains significant, OR 2.57(95%CI 1.23-5.36).Conclusion: In this study the R563Q mutation of the ß-subunit of the epithelial sodium channel gene was not linked to pre-eclampsia. No significant negative correlation could be established between the presence of the R563Q mutation and the outcomes of pre-eclampsia. Further research aimed at chronic hypertensive patients in pregnancy and unstable pre-eclampsia in larger study groups could shed more light on the relation between the mutation and the pre-eclamptic phenotype.

[发布机构] Stellenbosch University