An RGS2 3'UTR polymorphism is associated with preeclampsia in overweight women.
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ABSTRACT:
SUBMITTER: Karppanen T
PROVIDER: S-EPMC4997762 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
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An RGS2 3'UTR polymorphism is associated with preeclampsia in overweight women.
Karppanen Tiina T Kaartokallio Tea T Klemetti Miira M MM Heinonen Seppo S Kajantie Eero E Kere Juha J Kivinen Katja K Pouta Anneli A Staff Anne Cathrine AC Laivuori Hannele H
BMC genetics 20160824 1
<h4>Background</h4>Preeclampsia is a common and heterogeneous vascular syndrome of pregnancy. Its genetic risk profile is yet unknown and may vary between individuals and populations. The rs4606 3' UTR polymorphism of the Regulator of G-protein signaling 2 gene (RGS2) in the mother has been implicated in preeclampsia as well as in the development of chronic hypertension after preeclampsia. The RGS2 protein acts as an inhibitor of physiological vasoconstrictive pathways, and a low RGS2 level is a ...[more]
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Project description:BackgroundPreeclampsia 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.MethodsWe 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.ResultsNo 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.ConclusionWomen 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.
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Project description:Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly cholesterol metabolism, is associated with this disease. Liver X receptors alpha (NR1H3, also known as LXRalpha) and beta (NR1H2, also known as LXRbeta) play a key role in lipid metabolism. They belong to the nuclear receptor superfamily and are activated by cholesterol derivatives. They have been implicated in preeclampsia because they modulate trophoblast invasion and regulate the expression of the endoglin (CD105) gene, a marker of preeclampsia. The aim of this study was to investigate associations between the NR1H3 and NR1H2 genes and preeclampsia.We assessed associations between single nucleotide polymorphisms of NR1H3 (rs2279238 and rs7120118) and NR1H2 (rs35463555 and rs2695121) and the disease in 155 individuals with preeclampsia and 305 controls. Genotypes were determined by high-resolution melting analysis. We then used a logistic regression model to analyze the different alleles and genotypes for those polymorphisms as a function of case/control status.We found no association between NR1H3 SNPs and the disease, but the NR1H2 polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; p = 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; p = 0.049).This study provides the first evidence of an association between the NR1H2 gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease.
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Project description:Background:Preeclampsia (PE) is one of the main causes of maternal and perinatal mortality and morbidity. Evidence shows that oxidative stress plays an important role in the pathophysiology of the PE. As catalase is a key enzyme in antioxidant enzymatic defense which protects cell from oxidative damage, in this study, we aimed to investigate the relationship between CAT-21A/T (rs7943316) polymorphism and PE susceptibility. Materials and Methods:This case-control study was conducted on 155 PE women and 159 normotensive pregnant women. Polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping. Results:There was no association between CAT-21AT and TT genotypes and PE susceptibility. However, the CAT-21A/T polymorphism was associated with 1.6-fold higher risk of PE in dominant model (AA vs. AT + TT) (odds ratio [OR] 1.6 [95% confidence interval [CI]: 0.9-2.9]; P = 0.04). However, the CAT-21A/T polymorphism was not associated with PE in recessive model (TT vs. AA + AT) (OR 1.3 [95% CI: 0.8-2.1]; P = 0.4). Conclusions:The CAT-21A/T polymorphism could be a risk factor for PE susceptibility in dominant model.
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