Genetic analysis of factor V Leiden in a family with history of thrombosis and venous leg ulcers.

Inherited resistance to activated protein C has been recognized as a major risk factor for thrombosis. The factor V Leiden mutation, which is detectable by molecular DNA techniques, is responsible for 95% of cases of activated protein C resistance. In our study one patient with venous leg ulcers from a family with a history of thrombosis showed factor V Leiden mutation. Genotypic analysis demonstrated that the patient was homozygous for factor V Leiden. All family members of the index subject showed the same abnormalities. Two were homozygous and 3 were heterozygous for factor V Leiden mutation. The polymerase chain reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic digestion with MnlI for mutation detection. Patients with a family history of thrombosis and factor V Leiden have an increased risk of venous leg ulcers. Screening for factor V Leiden may be indicated in patients with venous leg ulcers and their family members.

Genetic analysis of angiotensinogen gene polymorphisms (M235T and T174M) in Romanian patients with essential arterial hypertension.

BACKGROUND: Several studies suggested the role of the genes of the rennin-angiotensin system in the pathogenesis of essential arterial hypertension. PATIENTS: We investigated 100 consecutive hypertensive patients (42 males and 58 females; mean +/- SD age, 55.14 +/- 9.49 years) for M235T and T174M polymorphisms. Seventy six normotensive patients (28 males and 48 females; mean +/- SD age, 54.94 +/- 9.56 years) formed the control group. METHODS: M235T and T174M polymorphisms were analyzed using PCR-RFLP methods. RESULTS: The carrier frequency of M235T polymorphism in the AGT gene was 73% in hypertensive patients and 34.21% in normotensive patients (OR 5.2, 95%CI [2.72-9.93], p<0.01, chi2 test). The carrier frequency of T174M polymorphism in the AGT gene was 42% in hypertensive patients and 11.84% in normotensive patients (OR 5.39, 95%CI [2.41-12.01], p<0.01, chi2 test). CONCLUSIONS: Essential arterial hypertension is associated with polymorphisms in the AGT gene, M235T and T174M.

Angiotensinogen gene M235T variant and pre-eclampsia in Romanian pregnant women.

BACKGROUND: Association between the human angiotensinogen gene and essential hypertension has been confirmed in recent studies. Pre-eclampsia is a complication of pregnancy characterised by increased vascular resistance, high blood pressure, proteinuria and oedema, that appears in the second and third trimester of pregnancy. The aim of our study was the analysis of M235T mutation in the gene encoding angiotensinogen in Romanian women with different forms of hypertension during pregnancy. METHODS: Fourteen women with obstetric complications were tested for M235T angiotensinogen gene mutation. Indications for testing were: severe or mild pre-eclampsia and pre-eclampsia associated with chronic hypertension. We also tested for control 6 healthy women. The M235T angiotensinogen gene mutation was analysed by polymerase chain reaction followed by enzymatic digestion with Tth 111I restriction endonuclease enzyme and agarose gel electrophoresis of the products. RESULTS: Eleven (78.57%) of the 14 women with complications of pregnancy had M235T mutation: 9 (64.28%) were found to be heterozygous carriers of the M235T variant of the angiotensinogen gene and 2 (14.28%) were found to be homozygous carriers. In the group of women with normal pregnancy, 3 (50%) of the 6 women had M235T mutation: 2 (33.33%) were found to be heterozygous carriers of the M235T variant of the angiotensinogen gene and 1 (16.66%) was found to be homozygous carrier. CONCLUSIONS: Our study shows that the M235T variant in the gene encoding angiotensinogen could be a risk factor in mild and severe pre-eclampsia.

Essential arterial hypertension and polymorphism of angiotensinogen M235T gene.

Several candidate genes, chosen from the renin- angiotensin system, were examined for their association with essential hypertension. The genes of the renin- angiotensin system (RAS) are good candidates for such an approach because this system is well known to be involved in the control of blood pressure. One of these candidate genes is the gene encoding for angiotensinogen (the most important gene of the RAS associated with essential hypertension in the most population, is the gene for angiotensin-converting enzyme- ACE). One DNA polymorphism within exon 2- with threonine instead of methionine at position 235 (M235T) was found to be significantly associated with hypertension. The objective of this study is the analysis of M235T polymorphism in angiotensinogen gene in Romanian patients with essential hypertension as well as controls. We examined 38 patients with essential hypertension and 21 normotensive patients. In order to identify the M235T angioteninogen variant, we used the following methods: DNA extraction, PCR amplification and enzymatic digestion of the PCR product using Tth 111I restriction endonuclease enzyme. In the study groups, the M235T variant (Met?Thr in aminoacid position 235) was found more frequently in hypertensive patients (81,57%), than in control subjects (66,66%). We identified 52,63% M235T heterozygotes in the hypertensive group compared with 47,61% in the control group, and 28,94% T235T homozygotes in the hypertensive group compared with 19,04% in the control group. The results of our study suggest an association of the M235T polymorphism in the gene encoding angiotensinogen with essential hypertension.