Hypertension after preeclampsia and relation to the C1114G polymorphism (rs4606) in RGS2: data from the Norwegian HUNT2 study

BMC Medical Genetics

Anne Cathrine Staff²  Ralf Dechend⁵  Hannele Laivuori³  Oddgeir L Holmen¹  Øyvind Melien⁴  Anne Stine Kvehaugen² 

[1] HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway;From the Department of Obstetrics and Department of Gynecology, Oslo University Hospital, Ulleval, Oslo, Norway and Faculty of Medicine, University of Oslo, Oslo, Norway;Haartman Institute, Medical Genetics, University of Helsinki Helsinki, Finland and Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland;The Norwegian Directorate of Health, Oslo, Norway;Experimental and Clinical Research Center, a joint cooperation between the Charite Medical Faculty and the Max-Delbrueck Center for Molecular Medicine and Helios Clinic Berlin-Buch, Berlin, Germany

关键词: Angiotensin II;    RGS2;    G proteins;    Polymorphism;    Hypertension;    Preeclampsia;   

Others  :  1092309
DOI  :  10.1186/1471-2350-15-28

 received in 2013-11-26, accepted in 2014-02-13,  发布年份 2014

【 摘 要 】

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-Trøndelag 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.

【 授权许可】

   
2014 Kvehaugen et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Steegers EA, von DP , Duvekot JJ, Pijnenborg R: Pre-eclampsia. Lancet 2010, 376:631-644.
• [2]ACOG Committee on Obstetric Practice: ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet 2002, 77:67-75.
• [3]Harskamp RE, Zeeman GG: Preeclampsia: at risk for remote cardiovascular disease. Am J Med Sci 2007, 334:291-295.
• [4]Bellamy L, Casas JP, Hingorani AD, Williams DJ: Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 2007, 335:974.
• [5]Tsang S, Woo AY, Zhu W, Xiao RP: Deregulation of RGS2 in cardiovascular diseases. Front Biosci (Schol Ed) 2010, 2:547-557.
• [6]Hercule HC, Tank J, Plehm R, Wellner M, da Costa Goncalves AC, Gollasch M, Diedrich A, Jordan J, Luft FC, Gross V: Regulator of G protein signalling 2 ameliorates angiotensin II-induced hypertension in mice. Exp Physiol 2007, 92:1014-1022.
• [7]Semplicini A, Lenzini L, Sartori M, Papparella I, Calo LA, Pagnin E, Strapazzon G, Benna C, Costa R, Avogaro A, Ceolotto G, Pessina AC: Reduced expression of regulator of G-protein signaling 2 (RGS2) in hypertensive patients increases calcium mobilization and ERK1/2 phosphorylation induced by angiotensin II. J Hypertens 2006, 24:1115-1124.
• [8]Kvehaugen AS, Melien O, Holmen OL, Laivuori H, Oian P, Andersgaard AB, Dechend R, Staff AC: Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia. Hypertension 2013, 61:655-661.
• [9]Holmen J, Midthjell K, Krüger Ø, Langhammer A, Holmen TL, Bratberg GH, Vatten L, Lund-Larsen PG: The Nord-Trøndelag Health Study 1995–97 (HUNT 2): Objectives, contents, methods and participation. Norsk Epidemiologi 2003, 13:19-32.
• [10]Thomsen LC, Klungsoyr K, Roten LT, Tappert C, Araya E, Baerheim G, Tollaksen K, Fenstad MH, Macsali F, Austgulen R, Bjorge L: Validity of the diagnosis of pre-eclampsia in the Medical Birth Registry of Norway. Acta Obstet Gynecol Scand 2013, 92:943-950.
• [11]Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003, 289:2560-2572.
• [12]Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D'Armiento J, Kris-Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CK, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, et al.: Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the american heart association. Circulation 2011, 123:1243-1262.
• [13]Craici I, Wagner S, Garovic VD: Preeclampsia and future cardiovascular risk: formal risk factor or failed stress test? Ther Adv Cardiovasc Dis 2008, 2:249-259.
• [14]Rankinen T, Bouchard C: Genetics and blood pressure response to exercise, and its interactions with adiposity. Prev Cardiol 2002, 5:138-144.
• [15]Magnussen EB, Vatten LJ, Lund-Nilsen TI, Salvesen KA, Davey SG, Romundstad PR: Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study. BMJ 2007, 335:978.
• [16]Magnussen EB, Vatten LJ, Smith GD, Romundstad PR: Hypertensive disorders in pregnancy and subsequently measured cardiovascular risk factors. Obstet Gynecol 2009, 114:961-970.
• [17]Cho H, Harrison K, Schwartz O, Kehrl JH: The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling. Biochem J 2003, 371:973-980.
• [18]Grant SL, Lassegue B, Griendling KK, Ushio-Fukai M, Lyons PR, Alexander RW: Specific regulation of RGS2 messenger RNA by angiotensin II in cultured vascular smooth muscle cells. Mol Pharmacol 2000, 57:460-467.
• [19]Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC: A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest 1973, 52:2682-2689.
• [20]Hladunewich MA, Kingdom J, Odutayo A, Burns K, Lai V, O’Brien T, Gandhi S, Zimpelmann J, Kiss A, Miller J, Cherney D: Postpartum assessment of the renin angiotensin system in women with previous severe, early-onset preeclampsia. J Clin Endocrinol Metab 2011, 96:3517-3524.
• [21]Saxena AR, Karumanchi SA, Brown NJ, Royle CM, McElrath TF, Seely EW: Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension 2010, 55:1239-1245.
• [22]Herse F, Staff AC, Hering L, Muller DN, Luft FC, Dechend R: AT1-receptor autoantibodies and uteroplacental RAS in pregnancy and pre-eclampsia. J Mol Med (Berl) 2008, 86:697-703.
• [23]Hubel CA, Wallukat G, Wolf M, Herse F, Rajakumar A, Roberts JM, Markovic N, Thadhani R, Luft FC, Dechend R: Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension 2007, 49:612-617.
• [24]Staff AC, Dechend R, Pijnenborg R: Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia-novel aspects for atherosclerosis and future cardiovascular health. Hypertension 2010, 56:1026-1034.
• [25]Kamide K, Kokubo Y, Yang J, Takiuchi S, Horio T, Matsumoto S, Banno M, Matayoshi T, Yasuda H, Miwa Y, Yoshihara F, Nakamura S, Nakahama H, Iwashima Y, Oguro R, Ohishi M, Rakugi H, Okamura T, Miyata T, Kawano Y: Association of intima-media thickening of carotid artery with genetic polymorphisms of the regulator of G-protein signaling 2 gene in patients with hypertension and in the general population. Hypertens Res 2011, 34:740-746.
• [26]Kurtze N, Rangul V, Hustvedt BE, Flanders WD: Reliability and validity of self-reported physical activity in the Nord-Trondelag Health Study (HUNT 2). Eur J Epidemiol 2007, 22:379-387.
• [27]Craig SR, Amin RV, Russell DW, Paradise NF: Blood cholesterol screening influence of fasting state on cholesterol results and management decisions. J Gen Intern Med 2000, 15:395-399.