Genetic polymorphisms of vascular endothelial growth factor [VEGF] in Egyptian women with breast cancer

Background: Vascular endothelial growth factor [VEGF] was considered to have an association with breast cancer because it regulates endothelial cell proliferation,migration and differentiation

Subjects and methods: One hundred and fifty two women with breast cancer were compared to 100 healthy control Egyptian women recruited from the same locality. VEGF gene polymorphisms were assessed using the PCR-RFLP analysis of DNA samples obtained from peripheral blood.SNP scanning was performed using MnII, BsmfI, CviAII, BsmfI, MnII restriction enzymes for VEGF1154 G/A, 634 G/C, 405 C/G, 936 C/T, 1612 G/A polymorphisms, respectively

Results: Breast cancer among Egyptian women was strongly associated with the mutations related to VEGF gene polymorphism as follows: VEGF 1154 G allele frequency was significantly higher than the A allele [P = 0.0007,O.R =2.4], VEGF 634 C allele frequency was significantly higher than the G allele [P = 0.012, O.R =0.62],VEGF 405 C Allele frequency was significantly higher than G Allele [P = 0.009, O.R =1.67], VEGF 936 C Allele frequency was significantly higher than the T Allele [P = 0.0057, O.R =1.72], VEGF 1612 G Allele frequency was significantly higher than A allele [P = 0.0148, O.R =1.62]. For VEGF 1154 GA: AA vs. GA+GG [Recessive] P = 0.10, O.R = 6.23, C.I [1.0-38.9], GA vs. AA+GG [over dominant] P= 0.01[*], O.R = 2.13, C.I [1.2-3.8], AA+GA vs. GG [dominant] P= 0.0015[*], O.R = 2.57, C.I [1.5-4.5]. For VEGF 634 GC: CC vs. GC+GG [Recessive] P= 0.1852, O.R = 0.64, C.I [0.4-1.2], GC vs. CC+GG [over dominant] P= 0.2669, O.R = 0.71, C.I [0.4-1.2], CC+GC vs. GG [dominant] P = 0.0002[**], O.R=0.05, C.I [0.0-0.2].For VEGF 405 CG: GG vs. CG+CC [Recessive] P= 0.0013[*], O.R = NA,C.I =NA, CG vs. GG+CC [over dominant] P= 0.877, O.R = 1.08, [0.6-1.9], GG+CG vs. CC [dominant] P = 0.0323[*], O.R=1.93,C.I [1.1-3.4].For VEGF 936 CT: TT vs. CT+CC [Recessive] P = 0.1833, O.R = 1.63, C.I [0.9-3.1], CT vs. TT+CC [over dominant] P = 0.1379, O.R = 1.55, C.I [0.9-2.6], TT+CT vs. CC[dominant] P = 0.0075[**], O.R=2.08, C.I [1.2-3.5]. For VEGF 1612 GA: AA vs. GA+GG [Recessive] P = 0.0000[**], O.R = NA, C.I = NA, GA vs. AA+GG [over dominant] P= 0.0002[**], O.R = 0.36, C.I [0.6-0.2], AA+GA vs. GG [dominant] P = 0.9541, O.R = 0.95, C.I [1.6-0.6]

Characterization of angiotensin converting enzyme gene polymorphism and risk of different heart diseases

The present work aims to test the association of angiotensin converting enzyme [ACE] gene insertion/ deletion [I/D] polymorphism in patients with myocardial infarction [MI]. The study comprised 79 Egyptian cases with MI. Their mean age was 54.4 +/- 9.9 years including 60 [75%] males and 19 [24.1%] females, 23 [29.1%] were smokers, 21 [26.6%] had a positive family history of MI, 25 cases [31.6%] were diabetic, 16 cases [20.3%] were hyperlipidemic. For comparison, 238 healthy subjects of nearly matched age and sex, with no history of any cardiac diseases were taken as a control group. For all subjects, DNA testing for ACE gene I/D polymorphism was done using PCR amplification to detect both D and I alleles followed by a second run PCR specific for the I allele for cases typed as DD in the first run. Cases had higher frequency of DD [29.1%] and ID [62%] than II [8.9%] genotype with a higher frequency of D allele than I allele [64.4% vs 33.6%]. Compared to controls, cases had significantly higher frequency of ID genotype [62% versus 47.5%, P < 0.05]. Cases with low risk factors had a higher frequency of ID genotype compared to controls [66.7% vs 47.5%, P = 0.002]. The same was, also, found in the high risk group but with a lower level of significance [63.6% vs 47.5%, P = 0.041]. ACE gene polymorphism is probably a risk factor for ischemic heart disease among Egyptian cases particularly if integrated with other environmental and genetic risk factors

Hemostatic markers of coagulopathy in acute promyelocytic leukemia

Hemostatic disorders are leading causes of death in patients with acute myeloid leukemia [AML] and particularly those with acute prom yelocytic leukemia [APL]. A contribution of fibrinolytic mechanisms has been claimed in the patho genesis of APL coagulopathy but investigations of the fibrinolytic activity of prom yelocytes have yielded conflicting results, sometimes based on reports of scattered [single] cases. The aim of this work is to study the changes of the different markers of thrombin generation and fibrinolysis in patients with APL and those with other AML subtypes [non APL-A ML], and to clarify the patho genesis of coagulopathy in patients with APL compard with those with non APL -A ML. The study included blood samples of 15 patients with APL and 25 patients with non APL-A ML, as well as 20 apparently healthy children with matched age and sex as a control group. Cases and controls were all subjected to the following investigations: pro thrombin concentration [PC], activated partial thromboplastin time [APTT], thrombin-anti thrombin complex [TAT], prothrombin fragment 1+2 [PF1+2], fibrinopeptide A [FPA], D-dimer, fibrinogen level, plasminogen activator inhibitor [PAI] and alpha 2-antiplasmin [alpha 2-AP]. As regards the markers of thrombosis PC was significantly lower in APL and AML in comparison to controls and in the same time it was significantly lower in APL in comparison to AML. PT, APTT, TAT, PF1+2, FPA and D-dimer levels in plasma of both APL and AML were significantly higher than controls and also it was found that these markers were significantly higher in APL than AML. About the fibrinolytic markers, fibrinogen was significantly lower in the cases of APL and AML than controls and it was found to be significantly lower in APL than AML. PAI and alpha 2-AP were significantly lower in APL and AML than controls but there was no significant difference between APL and AML. In the APL group a positive correlation was found between bone marrow promyelocyte% and D-dimer [r= 0.718, P< 0.003**] and between TAT and prepheral absolute promyelocyte [x10/L] [r=0.677, P< 0.006**]. In conclusion, acute myeloid leukemia in children, either APL or non-APL causes some changes in hemostatic mechanisms leading to acute DIC which was proved by the following tests: * Procoagulant activation which is proved by prolongation of APTT, PT, increased TAT, prothrombin fragment 1+2, fibrinopeptide A plasma levels as well as decreased prothrombin concentration and fibrinogen levels. * Fibrinolytic activation proved by decreased plasminogen activator inhibitor, alpha 2-antiplasmin plasma levels as well as increased plasma level of D-dimer which is a marker of plasmin activation. * Inhibitor consumption, proved by the study showed that the aforementioned laboratorial abnormalities were aggravated among cases with APL than those with non-APL-AML So DIC can be detected before bleeding