ABSTRACT
The aim of this work is to evaluate the prevalence of apolipoprotein-E [Apo E] gene polymorphisms in type-2 diabetes mellitus [DM] with coronary heart disease [CHD] and their influence on the severity of the disease, lipid profile and other risk factors [e.g. smoking, hypertension, body mass index and glycosylated hemoglobin Alc]. One hundred and twenty cases with type-2 DM were selected from those admitted to Internal Medicine and Cardiology Departments of Benha University Hospitals. Their ages ranged from 43 to 65 years [with a mean age of 52 +/- 8.2]. They were classified into 3 groups: group I included 30 diabetic cases with ischemic ECG changes, group II included 30 diabetic cases with myocardial infarction [Study groups] and group III included 60 diabetic cases without CHD [Control group]. Diagnosis of type 2 diabetes mellitus was made according to the criteria of American Diabetes Association. Diagnosis of CHD was determined from the history of angina pectoris, ischemic ECG changes, documented myocardial infarction, or major Q waves on a resting electrocardiogram. The Apo E4 patients showed the highest prevalence of CHD [71.4%], followed by Apo E3 patients [47.7%] and lastly Apo E2 patients [20%]. On comparison, there was a statistical significant difference between Apo E2 and Apo E4 genotype patients [P<0.05]; while the difference between Apo E2 and Apo E3 and between Apo E3 and Apo E4 genotype didn't yield statistical significant difference [P>0.05 respectively]. On the contrary Apo E2 patients showed the highest prevalence of non-CHD [80%], followed by Apo E3 [52.3%] and lastly Apo E4 [28.6%]. Regarding the distribution of Apo E genotypes among groups with CHD and those without CHD, there were no statistical significant differences between each Apo E genotypes [Apo E2, E3 and E4] in group I compared to group II [P>0.05 respectively], while there was a statistical significant difference between Apo E2 and Apo E3 patients in group III compared to group I and group II [P< 0.05 respectively]. Also, no statistical significant differences were found between different Apo E genotypes [Apo E2, E3 and E4] and other CHD risk factors [e.g. smoking, hypertension, BMI and HbA1c; P>0.05 respectively]. As regarding the relationship between lipid profile and Apo E genotype; the results were as follows: For serum cholesterol there was a highly significant difference between Apo E2 and each of Apo E4 and Apo E3 patients [P<0.05 respectively], while the difference between Apo E4 and Apo E3 patients [E4>E3] was not too big to give a statistical significance [P>0.05]. For serum low; density lipoprotein cholesterol [LDL-c], there was a highly significant difference between Apo E2 and Apo E4 patients [P<0.001], and significant differences between Apo E3 and each of Apo E2 and Apo E4 patients [P<0.05 and P<0.01 respectively]. For serum triglycerides[TGs] and serum high density lipoprotein cholesterol [HDL-c], the results of our study showed that Apo E2 and Apo E4 genotype patients had higher TGs and lower HDL-c levels in comparison to Apo E3 patients but the differences were statistically insignificant [P>0.05 respectively]. Apolipoprotein E gene polymorphism is an important risk factor for the development of CHD in type 2 diabetic patients, E4 allele plays as a risk factor and 82 allele plays as a protective factor. The role of 84 in the development of CHD is partly mediated by its effect on serum total cholesterol and LDL cholesterol levels. Farther studies on large number of patients with long term follow-up periods are needed to determine the relationship between epsilon 4 allele and severity of disease in CHD diabetic patients. Also further studies are recommended to know if epsilon 4 can act as a predicator of mortality in these patients and to explain the exact role of epsilon 4 allele in the development of CHD in type 2 diabetic patients; and the contribution of lipid profile and other CHD risk factors
Subject(s)
Humans , Male , Female , Apolipoproteins E , Coronary Disease , Polymorphism, GeneticABSTRACT
The aim of this study is to measure serum thrombopoietin [TPO] levels in patients with chronic active hepatitis C and post-hepatitis C liver cirrhosis, and examine the relationship between serum thrombopoietin concentration and the clinical stage of the disease, spleen index, circulating platelet counts, and liver functions in liver cirrhosis. One hundred and seventeen patients with chronic liver disease related to hepatitis C virus [44 with chronic active hepatitis C and 73 with liver cirrhosis] were selected, as a study group, from those admitted at the Internal Medicine Department of Benha University Hospitals. Their ages ranged from 37 to 62 years. Diagnosis of chronic active hepatitis C virus was based on the presence of positive HCV antibodies by 3[rd] generation ELISA [enzyme linked immunosorbant assay], abnormal elevation of serum transaminases for longer than 6 months, confirmed by positive HCV RNA by polymerase chain reaction [PCR] and liver biopsy which shows the stigmata of chronic hepatitis. Thirty healthy subjects were selected as a control group and matched with the study group regarding age, sex and residence. The mean levels of serum thrombopoietin in patients with chronic active hepatitis [CAH] were significantly higher than the control group [117.5 +/- 14.59 pg/ml, vs 99.8 +/- 11.03 pg/ml; P<0.001 respectively] while the mean levels of serum thrombopoietin were lower in cirrhotics than in CAH and the controls [82.82 +/- 20.7 pg/ml vs 117.5 +/- 14.59 pg/ml and 99.8 +/- 11.03 pg/ml; P<0.001 respectively]. In patients with liver cirrhosis, the mean levels of thrombopoietin decreased as the disease progressed [94.4 +/- 4.8 pg/ml in patients at Child-Pugh stage A, 73.4 +/- 10.5 pg/ml in patients at stage B and 45.1 +/- 5.6 pg/ml in patients at stage C] with statistical significant difference in-between them [P<0.001]. Thrombocytopenia [TCP] was found in 47 out of 73 [64.4%] of patients with liver cirrhosis. The mean levels of TPO in cirrhotics with TCP were significantly lower than cirrhotics without TCP [74.1 +/- 20.9 pg/ml vs 98.6 +/- 5.43 pg/ml; P<0.001]. Interestingly, in patients with liver cirrhosis, there was a correlation between serum TPO and the platelet counts [r = 0.826, P<0.001], but the spleen index did not exhibit correlation with the platelet counts and serum TPO [r = 0.036, r = - 0.103; P>0.05 respectively]. Serum TPO levels showed a negative correlation with total bilirubin, and a positive correlation with serum albumin and prothrombin concentration [r = - 0.915, r = 0.903, r = 0.856; P< 0.001 respectively]. The stepwise regression analysis showed that the prothrombin concentration, the serum albumin and the platelet count are the more significant variables with TPO [P<0.05]. It is concluded from this study that serum thrombopoietin levels increase in patients with chronic active hepatitis C, but in patients with liver cirrhosis, serum thrombopoietin levels decrease. As the liver disease progresses serum TPO decrease more. The impaired production of thrombopoietin may contribute to the development of thrombocytopenia in advanced stage of liver disease although increased splenic sequestration of platelets in the enlarged spleen may have an additional role. Since serum TPO is associated with liver function tests it is suggested that concentration of serum TPO is, to some degree, dependent on the capacity of the liver to produce this protein. It is prudent to speculate that the substitution of recombinant TPO in patients with cirrhosis will alleviate, if not cure, the thrombocytopenia observed in cirrhosis of the liver. Even more important, substitution of recombinant TPO could prevent bleeding complications by reducing the duration and extent of the platelet nadir after orthotopic liver transplantation