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Author Kvehaugen, A.S.; Melien, O.; Holmen, O.L.; Laivuori, H.; Dechend, R.; Staff, A.C. url  doi
  Title Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study Type Journal Article
  Year 2014 Publication BMC Medical Genetics Abbreviated Journal BMC Med Genet  
  Volume 15 Issue Pages 28  
  Keywords Adult; Case-Control Studies; Exercise; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Hypertension/epidemiology/*genetics; Norway; *Polymorphism, Single Nucleotide; Pre-Eclampsia/epidemiology/*genetics; Pregnancy; Prevalence; RGS Proteins/*genetics; Risk Factors; HUNT2  
  Abstract BACKGROUND: Preeclampsia is associated with an increased risk of hypertension later in life. The regulator of G protein signaling 2 negatively regulates several vasoconstrictors. We recently demonstrated an association between preeclampsia and the CG or GG genotype of the C1114G polymorphism (rs4606) of the regulator of G protein signaling 2 gene. Here, we examined the polymorphism with respect to the development of hypertension after pregnancy. METHODS: We genotyped 934 women on average 15.1 years after preeclampsia and 2011 age matched women with previous normotensive pregnancy. All women in this study were retrospectively recruited from the Nord-Trondelag Health Study (HUNT2). Information from HUNT2 was linked to the Medical Birth Registry of Norway to identify women with a history of preeclampsia and women without a history of preeclampsia. RESULTS: No significant association was found between hypertension (blood pressure >/=140/90 mmHg and/or taking antihypertensive drugs) and the polymorphism in crude analysis (OR (95% CI): CG genotype: 1.07 (0.90-1.27); GG genotype: 1.23 (0.90-1.67)). However, in a minimally adjusted model (age and BMI adjusted), a significant association between the GG genotype and hypertension was found (OR (95% CI): 1.49 (1.05-2.11)). This association remained significant also after adjustment for a history of preeclampsia (OR (95% CI): 1.46 (1.02-2.09)), but not in a model adjusted for multiple other variables (OR (95% CI): 1.26 (0.82-1.94)). In multivariate, but not in crude, analysis, the GG genotype of rs4606 (OR (95% CI): 1.93 (1.05-3.53)) was significantly and independently associated with severe hypertension later in life, defined as systolic blood pressure >/=160 mmHg (stage 2 hypertension) and/or taking antihypertensive drugs. A significant association was also found for the merged CG and GG genotypes (OR (95% CI): 1.43 (1.02-2.00)). Moreover, an interaction with physical activity was found. A history of preeclampsia was a significant and independent predictor of either definition of hypertension, both in crude and adjusted analyses. CONCLUSION: Women carrying the rs4606 CG or GG genotype are at elevated risk for developing hypertension after delivery. Physical activity may interact with the association. Preeclampsia remains an independent risk factor for subsequent hypertension after adjusting for this polymorphism and classical CVD risk factors.  
  Address From the Department of Obstetrics and Department of Gynecology, Oslo University Hospital, Ulleval, Oslo, Norway and Faculty of Medicine, University of Oslo, Oslo, Norway. UXNNAF@ous-hf.no  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2350 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24593135; PMC3973870 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1624  
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Author Kvehaugen, A.S.; Melien, O.; Holmen, O.L.; Laivuori, H.; Oian, P.; Andersgaard, A.B.; Dechend, R.; Staff, A.C. url  doi
  Title Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia Type Journal Article
  Year 2013 Publication Hypertension Abbreviated Journal Hypertension  
  Volume 61 Issue 3 Pages 655-661  
  Keywords Adult; Atherosclerosis/epidemiology/genetics; Biological Specimen Banks/statistics & numerical data; European Continental Ancestry Group/genetics/statistics & numerical data; Female; Gene Frequency; Genetic Predisposition to Disease/epidemiology; Heterotrimeric GTP-Binding Proteins/*genetics; Humans; Norway/epidemiology; Polymorphism, Genetic; *Polymorphism, Single Nucleotide; Pre-Eclampsia/epidemiology/*genetics; Pregnancy; Prevalence; RGS Proteins/*genetics; Receptor, Angiotensin, Type 1/genetics; Signal Transduction/*genetics; Young Adult  
  Abstract Preeclampsia is a pregnancy specific disorder and a risk factor for later cardiovascular disease. The cause and detailed pathophysiology remains unknown. G protein signaling is involved in a variety of physiological processes, including blood pressure regulation. We assessed whether distributions of 3 single nucleotide polymorphisms in genes coding for components of G protein signaling pathways that have been associated with hypertension differ between women with preeclampsia and normotensive pregnant women; the G protein beta3 subunit gene (GNB3) C825T polymorphism (rs5443), the angiotensin II type 1 receptor gene (AGTR1) 3'UTR A1166C polymorphism (rs5186), and the regulator of G protein signaling 2 gene (RGS2) 3'UTR C1114G polymorphism (rs4606). Two separate Norwegian study populations were used; a large population based study and a smaller, but clinically well-described pregnancy biobank. A descriptive study of 43 women with eclampsia was additionally included. In the population-based study, an increased odds of preeclampsia (odds ratio, 1.21; [95% confidence interval, 1.05-1.40]; P=0.009) and recurrent preeclampsia (odds ratio, 1.43; [95% confidence interval, 1.06-1.92];, P=0.017) was found in women carrying the rs4606 CG or GG genotype. In early-onset preeclamptic patients with decidual spiral artery biopsies available (n=24), the rs4606 CG or GG genotype was more frequent in those with acute atherosis (resembling early stage of atherosclerosis) compared with those without: odds ratio, 15.0; (95% confidence interval, 2.02-111.2); P=0.004. No association was found between preeclampsia and the rs5443 or the rs5186. The genotype distribution in eclamptic women was not different from preeclamptic women. In conclusion, RGS2 rs4606 may affect the risk and progression of preeclampsia.  
  Address Department of Obstetrics, Oslo University Hospital, Oslo, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0194-911X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23339167 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1432  
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