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 (PE) is a hypertensive disorder of pregnancy in which abnormal proliferation and apoptosis of placenta trophoblast has a pivotal role in its pathophysiology. The aim of the current study was to examine the association between Mouse Double Minute 2 (MDM2) T309G and 40 bp insertion/deletion (I/D) polymorphisms and PE risk.A case-control study was conducted on 208 PE women and 164 healthy pregnant women matching age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping.The MDM2 309GG genotype was associated with PE, and this genotype was found to be a risk factor for PE. There was no association between the MDM2 I/D polymorphism and PE. The haplotype-based association analysis revealed no association between MDM2 T309G and 40 bp I/D polymorphisms and PE. The frequency of TT-DD and GG-DD combined genotypes were significantly higher in PE women with marginal P values (P = 0.046).The MDM2 309GG genotype was associated with higher risk of PE. The TT-DD and GG-DD combined genotypes were higher in PE women.
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Project description:BackgroundPreeclampsia 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.MethodsWe 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.ResultsWe 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).ConclusionsThis 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:BackgroundPreeclampsia (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 methodsThis 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.ResultsThere 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).ConclusionsThe CAT-21A/T polymorphism could be a risk factor for PE susceptibility in dominant model.
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Project description:Preeclampsia affects 3% to 8% of pregnancies and increases risk of pregnancy-associated stroke (PAS). Data are limited on which women with preeclampsia are at highest risk for PAS.Using billing data from the 2003 to 2012 New York State Department of Health inpatient database, we matched women with preeclampsia and PAS 1:3 to preeclamptic controls based on age and race/ethnicity. Pre-defined PAS risk factors included pregnancy complications, infection present on admission, vascular risk factors, prothrombotic states, and coagulopathies. We constructed multivariable conditional logistic regression models to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for independent risk factors for PAS.Among women aged 12 to 55 years admitted to New York State hospitals for any reason during the study period (n=3?373?114), 88?857 had preeclampsia, and 197 of whom (0.2%) had PAS. In multivariable analysis, women with preeclampsia and stroke were more likely than controls to have severe preeclampsia or eclampsia (OR, 7.2; 95% confidence interval [CI], 4.6-11.3), infections present on admission (OR, 3.0; 95% CI, 1.6-5.8), prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5). Additional analyses matched and stratified by severity of preeclampsia confirmed these results.Infections, chronic hypertension, coagulopathies, and underlying prothrombotic conditions increase PAS risk in women with preeclampsia. These women may warrant closer monitoring.
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