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73 Genetic variability in oxidative stress-related gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) in preeclampsia and future cardiovascular risk
Abstracts / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 6 (2016) 137–177
Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives: To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods: A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56 and 97 days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results: The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Correlation between PAPP-A and PlGF MoM values was 0.21. Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions: PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes. doi:10.1016/j.preghy.2016.08.073
173
and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL and apolipoproteins A and B). For statistical analysis Student t-test and binary regression logistic were used. P < 0.05 was statistically significant. Results: We found lower PE risk associated to GSTT1 null (OR = 0.48; 95% CI = 0.25–0.96; P = 0.038) and an increased PE risk associated to MTHFR C carriers (OR = 4.18; 95% CI = 1.36–12.81; P = 0.012). The latter was also significantly associated to PE risk in a multivariate analysis (OR = 4.43; 95% CI = 1.41–3.14; P = 0.011). The two-way combination of GSTT1 non-null and MTHFR C carriers, adjusted for age, resulted in almost 3-fold increased PE risk (OR = 2.74; 95% CI = 1.20–6.69; P = 0.018). In the prospective cohort, for the GSTT1 non-null and MTHFR C carriers risk genotypes, we found that PE women that developed later hypertension, presented significantly higher levels of LDL in relation to those that became normotensive (138.53 ± 45.20 versus 104.16 ± 30.81; P = 0.025). NOS3 and GSTM1 polymorphisms were not associated to risk for PE. Conclusions: The present study indicates that oxidative stressrelated gene polymorphisms, namely, the association of GSTT1 non-null and MTHFR C carriers genotypes may be involved in susceptibility for preeclampsia. For this risk genetic model and according with the previously history of PE, these women may be more susceptible to future cardiovascular risk in premenopausal. doi:10.1016/j.preghy.2016.08.074
Clinical science 74 Association of sympathovagal imbalance with endothelial dysfunction in South Indian women with risk for pregnancyinduced hypertension – A follow-up study from a tertiary care hospital
Basic science 73 Genetic variability in oxidative stress-related gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) in preeclampsia and future cardiovascular risk Cardiovascular risks and metabolic diseases Andreia Matos a, Carolina Santos a, Alda Pereira Da Silva a, Maria José Areias b, Irene Rebelo c, Manuel Diamantino Bicho a (a Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina da Universidade Lisboa, Lisboa, Portugal, b Júlio Diniz Maternity, Maria Pia Hospital, Porto, Portugal, c Department of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal) Introduction: Preeclampsia (PE) may affect the risk for future cardiovascular disease. Oxidative stress and genetic polymorphisms associated to this pathway may modulate that risk through the antioxidant and anti-inflammatory differential effects of their genotypes. Objectives: To study the association between oxidative stressrelated gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) with the risk for preeclampsia and future cardiovascular risk. Methods: We evaluated 222 women, aged 35.11 ± 5.51 years, 124 (55.9%) with normal blood pressure in pregnancy and 98 (44.1%) with preeclampsia (PE). In a sub-sample of these, we also evaluated in a prospective study, 88 (62.9%) women that had previous PE 2 to 16 years ago. The GSTM1, GSTT1 and NOS3 a/b polymorphisms were determined by PCR and MTHFR C677T was determined by PCR-RFLP. In the prospective cohort, we studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein, myeloperoxidase, and nitric oxide metabolites (total and nitrites),
Gestational hypertension Subha Manivannan, Pravati Pal, Gopal Krushna Pal, Habeebullah Syed, Adithan Chandrasekaran, M.G. Sridhar (Jipmer, Puducherry, India) Introduction: Pregnancy-induced hypertension (PIH) is a serious medical complication with increasing incidence across the developing countries like India (5–15%). PIH is mainly characterised by widespread alteration and dysfunction in maternal vascular endothelium. But, whether the dysfunction is a cause or consequence of this multisystemic disorder has to be determined. Though the etiology of the disease is still indefinable, it is clear that it requires placenta to develop. Placental factors leads to extensive stimulation/dysfunction of the vascular endothelium, which in turn causes hypertension. The sympathetic activity is exaggerated in PIH even in the first trimester. Also sympathetic over activity plays a pathogenic role in stimulating hypertension and endothelial dysfunction. But so far no research have been conducted to explore the relationship between maternal endothelial factors and sympathovagal imbalance. Hence, in this study, we measured the degree of sympathetic activity and endothelial dysfunction in all the three trimesters to understand the causation of the disorder in pregnant women. Objectives: To study the association of sympathovagal imbalance (SVI) with endothelial dysfunction in pregnant women having a risk for PIH. Methods: This is a prospective longitudinal study. Subjects were initially divided into 2 groups: Control group (n = 50) and study group. Control group includes normotensive pregnant women and study group includes pregnant women with risk factors for PIH. Subjects were followed till term and incidence of PIH were noted.
Western European populations of Caucasian ethnicity. Differences in PAPP-A and PlGF concentrations by ethnicity have been observed, with increased levels in Afro-Caribbean, East Asian, and South Asian women. Baseline concentrations of sub-Saharan African women have not been evaluated. Objectives: To investigate PlGF and PAPP-A in a sub-Saharan African population and assess the performance of existing reference values of PAPP-A and PlGF. Methods: A nested cross-sectional study was conducted in two public hospitals in Accra, Ghana. Out of the original 1010 women enrolled in the cohort, 398 participants were eligible for inclusion with a normotensive singleton gestation and serum samples taken between 56 and 97 days of pregnancy. PAPP-A and PlGF concentrations were measured with an automated immunoassay. Multiple of the median (MoM) values corrected for gestation and maternal weight for PAPP-A and PlGF were calculated using reference values of a Dutch perinatal screening laboratory based on over 10.000 samples, and PlGF manufacturer reference values, respectively. Results: The PAPP-A median MoM was 2.34 (interquartile range (IQR) 1.24–3.97). Median PlGF MoM was 1.25 (IQR 0.95–1.80). Correlation between PAPP-A and PlGF MoM values was 0.21. Median MoM values for PAPP-A and PlGF tended to be slightly different for various Ghanaian ethnic subgroups. Conclusions: PAPP-A and PlGF MoM values appear to be substantially higher in a sub-Saharan African population compared to the Caucasian or Afro-Caribbean MoM values previously reported. The difference suggests the need for a specific correction factor for this population to avoid underestimation of risk for fetal aneuploidies or placental disorders when using PAPP-A and PlGF MoM for screening purposes. doi:10.1016/j.preghy.2016.08.073
173
and others associated with liver function (AST and ALT) and lipid profile (total LDL and cholesterol HDL, non-HDL and apolipoproteins A and B). For statistical analysis Student t-test and binary regression logistic were used. P < 0.05 was statistically significant. Results: We found lower PE risk associated to GSTT1 null (OR = 0.48; 95% CI = 0.25–0.96; P = 0.038) and an increased PE risk associated to MTHFR C carriers (OR = 4.18; 95% CI = 1.36–12.81; P = 0.012). The latter was also significantly associated to PE risk in a multivariate analysis (OR = 4.43; 95% CI = 1.41–3.14; P = 0.011). The two-way combination of GSTT1 non-null and MTHFR C carriers, adjusted for age, resulted in almost 3-fold increased PE risk (OR = 2.74; 95% CI = 1.20–6.69; P = 0.018). In the prospective cohort, for the GSTT1 non-null and MTHFR C carriers risk genotypes, we found that PE women that developed later hypertension, presented significantly higher levels of LDL in relation to those that became normotensive (138.53 ± 45.20 versus 104.16 ± 30.81; P = 0.025). NOS3 and GSTM1 polymorphisms were not associated to risk for PE. Conclusions: The present study indicates that oxidative stressrelated gene polymorphisms, namely, the association of GSTT1 non-null and MTHFR C carriers genotypes may be involved in susceptibility for preeclampsia. For this risk genetic model and according with the previously history of PE, these women may be more susceptible to future cardiovascular risk in premenopausal. doi:10.1016/j.preghy.2016.08.074
Clinical science 74 Association of sympathovagal imbalance with endothelial dysfunction in South Indian women with risk for pregnancyinduced hypertension – A follow-up study from a tertiary care hospital
Basic science 73 Genetic variability in oxidative stress-related gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) in preeclampsia and future cardiovascular risk Cardiovascular risks and metabolic diseases Andreia Matos a, Carolina Santos a, Alda Pereira Da Silva a, Maria José Areias b, Irene Rebelo c, Manuel Diamantino Bicho a (a Genetics Laboratory and Environmental Health Institute, Faculdade de Medicina da Universidade Lisboa, Lisboa, Portugal, b Júlio Diniz Maternity, Maria Pia Hospital, Porto, Portugal, c Department of Biochemistry, Faculty of Pharmacy, University of Porto, Porto, Portugal) Introduction: Preeclampsia (PE) may affect the risk for future cardiovascular disease. Oxidative stress and genetic polymorphisms associated to this pathway may modulate that risk through the antioxidant and anti-inflammatory differential effects of their genotypes. Objectives: To study the association between oxidative stressrelated gene polymorphisms (GSTM1, GSTT1, NOS3 and MTHFR) with the risk for preeclampsia and future cardiovascular risk. Methods: We evaluated 222 women, aged 35.11 ± 5.51 years, 124 (55.9%) with normal blood pressure in pregnancy and 98 (44.1%) with preeclampsia (PE). In a sub-sample of these, we also evaluated in a prospective study, 88 (62.9%) women that had previous PE 2 to 16 years ago. The GSTM1, GSTT1 and NOS3 a/b polymorphisms were determined by PCR and MTHFR C677T was determined by PCR-RFLP. In the prospective cohort, we studied demographic, anthropometric, and haemodynamic biomarkers such as C-reactive protein, myeloperoxidase, and nitric oxide metabolites (total and nitrites),
Gestational hypertension Subha Manivannan, Pravati Pal, Gopal Krushna Pal, Habeebullah Syed, Adithan Chandrasekaran, M.G. Sridhar (Jipmer, Puducherry, India) Introduction: Pregnancy-induced hypertension (PIH) is a serious medical complication with increasing incidence across the developing countries like India (5–15%). PIH is mainly characterised by widespread alteration and dysfunction in maternal vascular endothelium. But, whether the dysfunction is a cause or consequence of this multisystemic disorder has to be determined. Though the etiology of the disease is still indefinable, it is clear that it requires placenta to develop. Placental factors leads to extensive stimulation/dysfunction of the vascular endothelium, which in turn causes hypertension. The sympathetic activity is exaggerated in PIH even in the first trimester. Also sympathetic over activity plays a pathogenic role in stimulating hypertension and endothelial dysfunction. But so far no research have been conducted to explore the relationship between maternal endothelial factors and sympathovagal imbalance. Hence, in this study, we measured the degree of sympathetic activity and endothelial dysfunction in all the three trimesters to understand the causation of the disorder in pregnant women. Objectives: To study the association of sympathovagal imbalance (SVI) with endothelial dysfunction in pregnant women having a risk for PIH. Methods: This is a prospective longitudinal study. Subjects were initially divided into 2 groups: Control group (n = 50) and study group. Control group includes normotensive pregnant women and study group includes pregnant women with risk factors for PIH. Subjects were followed till term and incidence of PIH were noted.