angiotensinogen and Thrombophilia

The aim: To study the distribution and influence of coagulation factor gene polymorphisms, endothelial dysfunction, blood pressure regulator on the development of obstetric and perinatal complications in women with preeclampsia (PE).. Materials and methods: The prospective cohort study included 46 women with PE and maternal or fetal complications and 87 pregnant women with PE, without complications. Genetic polymorphisms of coagulation factors and fibrinolysis (1691 G→A FVL, 20210 G→A prothrombin, 675 5G/4G PAI-1, 455 G→A fibrinogen β), endothelial dysfunction (192 Q→R PON-1, 677 C→T MTHFR) and blood pressure regulator (235 M→T angiotensinogen II) were studied with the help of allele-specific polymerase chain reaction.. Results: Markers of predisposition to the development of obstetric and perinatal complications in pregnant women with PE are the following genotypes: 1691 GA by V Leiden factor gene - increases the risk in 2.9 times (95% CI 1.94-4.33), 20210 GA by prothrombin gene - in 2.36 times (95% CI 1.54-3.6), 20210 AA by prothrombin gene - in 3.12 times (95% CI 2.4-4.0). Pathological polymorphisms in the genes of angiotensinogen II 235 M→T, PAI-1 5G/4G, fibrinogen β 455 G→A, paraoxonase-1 192 Q→R do not significantly affect the development of complications during preeclampsia.. Conclusions: The development of PE against the background of the existence of acquired and hereditary types of thrombophilia is associated with a more severe course, early-onset and the development of life-threatening complications for a mother and fetus.

Topics: Angiotensinogen; Factor V; Female; Fibrinogen; Humans; Placenta; Plasminogen Activator Inhibitor 1; Pre-Eclampsia; Pregnancy; Pregnant Women; Prospective Studies; Prothrombin; Thrombophilia

Inflammatory bowel disease (IBD) is linked to a definite risk of thromboembolic events (TE), but data on the role of prothrombotic genetic mutations are conflicting.. Fourteen genetic factors involved in TE pathogenesis were investigated in a homogeneous cohort of Sicilian patients with IBD with and without history of TE and in healthy controls. Forty IBD patients (21 CD, 19 UC) and 20 healthy individuals were enrolled. Genetic testing was based on the reverse hybridization principle by a commercial assay that analyzes 14 polymorphisms involved in thrombophilia and cholesterol metabolism. The rate of genetic polymorphisms and mutations was compared between IBD patients and healthy controls.. No significant difference in allelic frequency was found between IBD patients and controls except AGT T/T, though a trend toward significance was found also for ACE D/D. Eight out of 9 patients with earlier history of TE had more than 1 polymorphism, compared with 12 out of 31 without TE. In patients with IBD the mutation AGT T/T was related to male sex (P<0.0259) and, marginally, to arterial hypertension (P<0.06) and diabetes (P<0.09).. Our data confirm a definite risk of TE in IBD (22.5% of our series). An increased frequency of the genotypes ACE D/D and AGT T/T, never reported so far, was found. In IBD patients TE has a multifactorial genesis with involvement of several genes as well and acquired factors. Genetic screening for prothrombotic factors could help segregate IBD patients at higher risk of TE.

Topics: Adult; Aged; Angiotensinogen; Female; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases; Male; Middle Aged; Mutation; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Risk Factors; Sicily; Thrombophilia

Several polymorphisms related to hypertension, thrombophilia, and oxidative stress has been associated with the development of cardiovascular disease. We analyzed the frequency of M235T angiotensinogen (AGT), A222V 5,10 methylenete-trahydrofolate reductase (MTHFR), L33P glycoprotein IIIa (GPIIIa), and I105V glutathione S-transferase P1 (GSTP1)} polymorphisms in 285 individuals belonging to Mexican-Mestizo and five Amerindian population from México, by real time PCR allelic discrimination. Allele and genotype frequencies were compared using chi square tests. All populations followed the Hardy Weinberg equilibrium for assay markers with the exception of the Triki, whose were in Hardy Weinberg dysequilibrium for the glutathione S-transferase P1 polymorphism. Interestingly, according to all the analyzed single nucleotide polymorphisms (SNPs), the Triki population was the most differentiated and homogeneous group of the six populations analyzed. A comparison of our data with those previously published for some Caucasian, Asian and Black populations showed quite significant differences. These differences were remarkable with all the Mexican populations having a lower frequency of the 105V allele of the glutathione S-transferase P1 and reduced occurrence of the 222A allele of the 5,10 methylenetetrahydrofolate reductase. Our results show the genetic diversity among different Mexican populations and with other racial groups.

Topics: Adolescent; Adult; Angiotensinogen; Asian People; DNA; Gene Frequency; Genetic Predisposition to Disease; Genotype; Glutathione S-Transferase pi; Humans; Hypertension; Indians, North American; Integrin beta3; Methylenetetrahydrofolate Reductase (NADPH2); Mexico; Middle Aged; Oxidative Stress; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Risk Factors; Thrombophilia; White People; Young Adult

The purpose of this study was to analyze functional polymorphisms in candidate genes (methylenetetrahydrofolate reductase [MTHFR]677C>T, MTHFR1298A>C, factor 5 1691G>A [FVL], and angiotensinogen (AGT)-6G>A) in relation to a hypothesized placental hemorrhage pathway to preterm delivery (PTD).. We assessed maternal genotypes, pregnancy outcomes, and placental pathologic evidence among 560 white and 399 black women who were recruited at mid trimester into a prospective cohort study (1998-2004). Odds of dominant genotypes were calculated for PTDs with (n = 56) or without (n = 177) evidence of placental hemorrhage (referent = term) with the use of race-stratified polytomous logistic regression models.. Among white women, FVL GA/AA and AGT(-6) GA/AA were both associated with hemorrhage-related PTDs (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.6-14.2 and OR, 3.8; 95% CI, 1.3-10.5, respectively), but not other PTDs (ORs, 1.2 and 0.9, respectively). FVL GA/AA was associated with placental abruption (OR, 5.8; 95% CI, 1.1-30) among white women. All results were null for MTHFR genotypes.. FVL and AGT variant genotypes were associated specifically with hemorrhage-related PTDs.

Topics: Adult; Angiotensinogen; Factor V; Female; Gene Frequency; Genotype; Hemorrhage; Humans; Logistic Models; Methylenetetrahydrofolate Reductase (NADPH2); Placenta Diseases; Point Mutation; Polymorphism, Genetic; Pregnancy; Pregnancy Outcome; Premature Birth; Renin-Angiotensin System; Thrombophilia; Young Adult