Genotype of the CYBA promoter − 930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: An observational study

Background and objective. Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). Material and methods: We studied the −930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). Results: The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE (P=0.03). A higher frequency of ∈3/∈4 and ∈4/∈4 genotypes of APOE was observed in patients with PE or NPH compared with controls (P<0.01). There were no significant differences detected in genotype or allele distribution of the MTHFR, C677T polymorphism. APOE ∈3/∈4 and ∈4/∈4 genotypes had a worse lipoprotein profile characterized by higher plasma values of total cholesterol (P<0.05) and triglycerides (P<0.005). Despite no differences in MTHFR C677T polymorphism distribution, higher levels of plasma homocysteine were observed in patients with PE than in patients with NPH or controls. Conclusions: CYBA and APOE polymorphism showed a different distribution in the groups studied, while no differences were observed in MTHFR C677T polymorphism. APOE genotype was associated with changes in lipid and lipoprotein profiles in pregnant women (AU)

Fundamento y objetivo: Nos propusimos valorar en un estudio observacional si algunos polimorfismos en genes que regulan el estrés oxidativo, los niveles de homocisteina y el metabolismo de los lípidos, podrían predisponer a diferentes trastornos hipertensivos del embarazo. Material y métodos: Estudiamos el polimorfismo −930A/G del gen promotor del CYBA, el genotipò de la apolipoproteína E (ApoE) y el polimorfismo C677T del gen de la metilen tetrahidrofolato-reductasa (MTHFR) en 134 embarazadas sanas, 266 embarazadas con hipertensión no proteinurica (HNP) y 184 pacientes con preeclampsia (PE). Resultados: El genotipo GG del promotor del gen del CYBA estuvo presente en el 32,1% de la población de control, en el 38,7% de las pacientes con HNP (p=0,19) y el 21,2% de las mujeres con PE (p=0,03). Los pacientes con PE o HNP, en comparación con los controles, mostraron una mayor frecuencia de genotipos ∈3/∈4 y ∈4/∈4 (p<0,01). No hubo diferencias significativas en la distribución por genotipos del polimorfismo C677T del gen de la MTHFR. Los genotipos ∈3/∈4 y ∈4/∈4 de la ApoE mostraron un peor perfil lipoproteico caracterizado por un aumento de colesterol total (p<0,05) y triglicéridos (p<0,005). A pesar de no haber diferencias en la dsitribución de la mutación C677T del gen de la MTHFR, se observó un aumento de los niveles de homocisteína plasmática en los pacientes con PE. Conclusiones: Los polimorfismos del gen del CYBA y de la ApoE mostraron una distribución diferente en los grupos estudiados que no se observó en el prolimorfismo C677T del gen MTHFR (AU)

Genotype of the CYBA promoter -930A/G, polymorphism C677T of the MTHFR and APOE genotype in patients with hypertensive disorders of pregnancy: an observational study.

BACKGROUND AND OBJECTIVE: Hypertensive disorders of pregnancy could be favoured by polymorphisms in genes affecting vascular physiology. The aim of our work was to study several variants in the genes regulating oxidative stress, plasma lipids metabolism and endothelial function (observational study). MATERIAL AND METHODS: We studied the -930A/G polymorphism of the CYBA gene promoter, the apolipoprotein E (APOE) genotype and the methylene-tetrahydrofolate reductase (MTHFR) gene C677T polymorphism in 134 healthy pregnant women, 266 pregnant with non-proteinuric hypertension (NPH) and 184 patients with preeclampsia (PE). RESULTS: The GG genotype of the CYBA gene promoter was present in 32.1% of the control population, 38.7% of patients with NPH (P=0.19) and 21.2% of the women with PE (P=0.03). A higher frequency of epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes of APOE was observed in patients with PE or NPH compared with controls (P<0.01). There were no significant differences detected in genotype or allele distribution of the MTHFR, C677T polymorphism. APOE epsilon 3/epsilon 4 and epsilon 4/epsilon 4 genotypes had a worse lipoprotein profile characterized by higher plasma values of total cholesterol (P<0.05) and triglycerides (P<0.005). Despite no differences in MTHFR C677T polymorphism distribution, higher levels of plasma homocysteine were observed in patients with PE than in patients with NPH or controls. CONCLUSIONS: CYBA and APOE polymorphism showed a different distribution in the groups studied, while no differences were observed in MTHFR C677T polymorphism. APOE genotype was associated with changes in lipid and lipoprotein profiles in pregnant women.

Glucose effectiveness is strongly related to left ventricular mass in subjects with stage I hypertension or high-normal blood pressure.

BACKGROUND: Evidence suggests that "glucose effectiveness," (SG) or the effect of glucose per se to enhance net glucose disposal, may be at least as important as the insulin sensitivity index (SI) in the assessment of glucose tolerance. Our objective was to study the relationship of SG and SI parameters to left ventricular mass in a group of untreated, nondiabetic, and nonobese subjects recently diagnosed with stage I or high-normal blood pressure (BP). METHODS: In this sample of subjects, among whom the expected prevalence of insulin resistance is low, we assessed SG and SI parameters using the intravenous glucose tolerance test and minimal model analysis. We also measured left ventricular mass (LVM) index and diastolic function by echocardiography. RESULTS: We observed a strong relationship between SG and LVM index (r = -0.61, P <.0001). Patients with left ventricular hypertrophy (LVH) had lower SG than those without LVH (0.1114 +/- 0.04 v 0.2088 +/- 0.08 x 10(-1). min(-1), P <.001). In contrast, patients below the lowest quartile of the SG parameter distribution had higher LVM index (126.4 +/- 23.1 v 94.8 +/- 22.3 g/m(2), P <.001) and also had higher prevalence of LVH than the other patients (P <.0001). The SI related only to diastolic dysfunction, suggesting that SG may be an earlier marker of LVH than SI in hypertension. CONCLUSION: In this sample of nonobese and glucose-tolerant subjects with an early stage of hypertension, SG but not SI was related to LVM.

Role of ketoconazole treatment in urinary-free cortisol-to-cortisone and tetrahydrocortisol-to-tetrahydrocortisone ratios in nonectopic Cushing's syndrome.

We hypothesized that in nonectopic Cushing syndrome there is an insufficient activity of type II (renal) 11beta-hydroxysteroid dehydrogenase (11beta-HSD2) that is related to cortisol excess, rather than to corticotropin (adrenocorticotropic hormone [ACTH]) levels. We measured plasma ACTH and urinary-free cortisol (UFF), urinary-free cortisone (UFE), tetrahydrocortisol (UTHF), and tetrahydrocortisone (UTHE) in 24-h urine samples of 24 healthy subjects and 15 patients diagnosed with nonectopic Cushing syndrome. Then, in the group of patients, a new 24-h urine sample was collected after treatment with 800 mg daily of ketoconazole. The UFF/UFE and UTHF/UTHE ratios were calculated as an estimation of 11beta-HSD2 activity. The patients had an increase in both the UFF/UFE (19.95 +/- 10.3 vs 5.78 +/- 4.72 nmol/24 h; p < 0.0001) and UTHF/UTHE ratios (5.36 +/- 5.23 vs 1.39 +/- 0.95 nmol/24 h; p < 0.001). Both UFF/UFE and UTHF/UTHE ratios decreased after ketoconazole treatment (19.95 +/- 10.3 vs 12.2 +/- 6.9 nmol/24 h; p < 0.005; and 5.36 +/- 5.23 vs 1.62 vs 1.21 nmol/24 h; p < 0.001, respectively). The control subjects had a significant relationship between UFF and UFE (r = 0.70, p < 0.0001), and between UTHF and UTHE (r = 0.75, p < 0.0001) that did not exist in the patient group. After ketoconazole treatment, the decrease in cortisol excretion in the patient group allowed a positive and significant relation between UFF and UFE (r = 0.64, p < 0.01) and between UTHF and UTHE (r = 0.56, p < 0.05) to appear. There was not any significant relationship between either UFF/UFE or UTHF/UTHE ratios and plasma levels of ACTH.

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension]. / Polimorfismos genéticos del sistema renina-angiotensina e hipertensión arterial esencial.

BACKGROUND: The renin-angiotensin system (RAS) is known to regulate the blood pressure (BP). Several RAS polymorphisms have been associated with essential hypertension (EH), but there is uncertainty about this association. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T polymorphism of the angiotensinogen (AGT) gene were associated with EH in a sample of Spanish hipertensive patients. PATIENTS AND METHOD: We studied 1,204 patients with EH (BP > 140/90 mmHg): 668 males, aged 50.8 (13.6) years with systolic BP 151.7 (19.1) and diastolic BP 94.3 (13) mmHg [mean (SD)] and 536 females, aged 52.4 (13.9) years with systolic BP 155.1 (19.8) and diastolic BP 94.5 (12.3) mmHg. As a control group, 367 men and 280 women with no family history of cardiovascular disease who had a normal blood pressure were included. Polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphism. RESULTS: The genotype distribution and allele frequencies of the two RAS polymorphisms were similar in hypertensive and control subjects. Similarly, there were no differences in BP level with regard to the genotype in male or female patients. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive subjects. CONCLUSIONS: This study suggests that in the population studied, the contribution of the ACE I/D polymorphism and the AGT M235T polymorphism in the development of EH is less important than previously estimated.

Simvastatin improves endothelial function in spontaneously hypertensive rats through a superoxide dismutase mediated antioxidant effect.

BACKGROUND: Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitors have beneficial effects beyond their cholesterol-lowering properties. The antioxidant mechanism of HMGCoA reductase inhibitors is not completely understood. OBJECTIVES: To elucidate the antioxidant effect of simvastatin. METHODS: We studied the influence of simvastatin treatment on the development of hypertension, modification of antioxidant systems, and reactivity of aortic rings in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. RESULTS: Simvastatin had no effect on blood pressure (BP). Simvastatin treatment (either 1 or 2 mg/kg body weight for 12 or 20 weeks) increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in SHR rats compared with untreated control SHR rats. Carbachol-induced relaxation of aortic rings was impaired in control SHR rats and was restored by simvastatin treatment. Addition of SOD improved the response in control SHR rats and did not have any effect in treated SHR rats. Addition of diethyldithiocarbamic acid, a selective inhibitor of SOD, produced a mild non-significant impairment in carbachol-induced relaxation in control SHR rats, suggesting a deficient antioxidant system in these animals. However, in treated SHR and in WKY rats, impairment of the relaxation was marked, implying that SOD activity in these animals was important to maintain endothelial function. In aortic rings without endothelium from SHR rats, contraction induced by free radicals was substantially higher than in WKY rats. This effect was attenuated in 1-mg-treated rats and abolished in 2-mg-treated rats. CONCLUSIONS: Simvastatin promotes intracellular antioxidant systems, fundamentally SOD, restoring endothelial function but not having any effect on blood pressure.

Prevalencia de dislipemia y de sus distintos fenotipos en la hipertensión arterial esencial de comienzo reciente / Prevalence of dyslipidemia and its phenotypes in recently diagnosed essential arterial hypertension

Fundamento: Conocer la prevalencia de fenotipos dislipémicos, frecuencia y características clinicometabólicas en pacientes hipertensos de diagnóstico reciente. Métodos: Estudio de 158 casos consecutivos de hipertensos esenciales sin tratamiento farmacológico. Resultados: El 69,6 por ciento de los pacientes presentaban alguna forma de dislipemia, el aumento aislado de Lp(a) (27,3 por ciento) es la más prevalente y la menos la hiperapobetalipoproteinemia (10,0 por ciento). La edad, el sexo, el tabaquismo, la ingestión alcohólica, la presión arterial sistólica, del pulso, ácido úrico y glucemia basal fueron diferentes en cada fenotipo. Conclusiones: La prevalencia de alguna forma de dislipemia en la hipertensión arterial esencial es muy elevada y heterogénea (AU)