Patterns of thrombospondin genes polymorphisms in acute myocardial infarction patients in Ismailia City

Thrombospondin [TSP] 2 and 4 are multidomain calcium-binding extracellular glycoproteins which play a role in platelet aggregation and inflammatory response. TSP-2 has chemotactic and mitogenic activities for vascular smooth muscle cells while TSP-4 mRNA is expressed by endothelial and smooth muscle cells in vascular wall, and brain endothelial cells produce the protein both in vivo and in cell culture, localization consistent with its pro-atherogenic effects. These common functions may be central to the roles of the thrombospondins in coronary artery disease and myocardial infarction [MI]. In the present study, the association of the TSP-2[3949 T-+G, rs8089] and TSP-4 [Ala387Pro 1186 G-+C, rs866389] gene variations and MI among Egyptian patients living in Ismailia city has been examined. Both rs8089 and rs 1866389 were studied in 50 acute MI patients and 50 controls using Real-Time polymerase chain reaction. The prevalence of TSP-2 and TSP-4 alleles was not different in MI patients compared to controls [P> 0.05]. Although the minor allele homozygotes [GG] of TSP-2 seems to confer reduced risk of MI [OR: 0.42 95% CI=0.095-1.89] this was not statistically significant [P> 0.05]. The distribution of different TSP-4 genotypes did not differ between MI patients and controls [P>0.05]. Total cholesterol was statistically significantly higher [P=Q.Q2] in carriers of minor allele [C] of TSP4 [GC+CC]. Although, both polymorphisms showed no statistically significant difference in MI patients regarding all other measured conventional risk factors. However, the frequency of TTGC haplotype is statistically significantly higher in MI patients [24%] than in controls [6%] [P value=0.0226]. Our data suggests that although association analysis with MI did not reach significance, an at-risk haplotype of common variants located in THBS2 and THBS4 may be part of the genetic determinants for MI in the Egyptian population living in Ismailia city

Effect alpha globlin gene deletion and gamma globin gene -158 [C/T] polymorphism in beta-thalassemic patients

The beta-thalassemias [beta- thalassemias] are among the most common autosomal recessive disorders. They have a remarkably high frequency in the Mediterranean region and represent one of the most common genetic diseases in Egypt. In this study, the spectrum of beta-thalassemia mutations and genotype-to-phenotype correlations were defined in 32 beta- thalassemic patients [beta- thlassemias major and intermedia] with varying disease severity in two cities of the Suez Canal region. Ten different mutations were identified and the most frequent ones were: IVSI-6 [T-C] [37.5%], IVSI-110 [G-A] [34.4%] and both IVSI-1 [G-A], IVSII-745 [C-G] and -102 [C-G] [12.5% each]. There was a wide spectrum of phenotypic severity in all patients. We studied the Xmnl polymorphism [C/T] in gamma- globin gene position -158 of beta- thalassemia as a modulating factor of the disease severity. Presence of the polymorphism was found in two patients and this was not sufficient to explain the diversity of the phenotype encountered. Co-inheritance of alpha thalassaemia as a modulating factor was not evident in our patients. In conclusion, we have been unable to find a molecular basis for the benign clinical course in all our patients. Other genetic or acquired factors must be hypothesized which ameliorate the clinical condition

C-Reactive protein, Tumor Ncrosis Factor-alpha, interleukin-6 and cortisol in type 2 diabetes mellitus

Recently an abundance of evidence has emerged demonstrating a close link between immunity, inflammation, obesity, insulin resistance and type 2 diabetes mellitus. Activation of innate immunity with production of inflammatory markers was suggested to provide a new model for the pathogenesis of type 2 diabetes and the metabolic syndrome. This may result in new approaches for predicting and managing of type 2 diabetes and its complications. We evaluated the state of obesity and diabetes mellitus of thirty nine male type 2 diabetic patients and nineteen age-matched male healthy subjects as control. This evaluation was performed via assessment of the body mas index [BMI], fasting and postprandial [PP] blood glucose and insulin, insulin resistance and fasting C-peptide. Then we assessed the plasma levels of the most important inflammatory markers; C-reactive protein [C-RP], tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6] and the total leucocytic count as well as the stress hormone cortisol. Our results showed BMI above 30 for both patients and controls which indicated obesity of the two groups. Both fasting and PP glucose were 167.9 +/- 10.3 and 289.8 +/- 16 mg/dl respectively for patients and 96.4 +/- 1.96 and 108.47 +/- 4.6 rng/dl respectively for the control whish confirmed the diagnosis of diabetes mellitus. The C-RP was significantly higher in diabetics. Although the difference did not reach statistical significance fasting and PP-insulin, insulin resistance levels were higher in the diabetic patients compared to the control. Regarding the results of the acute phase reactants and the biornarkers for inflammation, we found a significant increase in C-RP, TNF-alpha, IL-6 and cortisol in the diabetic patients compared to the control. But no change could be detected in the total leucocytic count. This association between hyperglycemia and increased inflammatory markers may indicate a relationship between them. But the question which of them preceded and led to the other is still uncertain. Further studies with different approaches may be needed to solve this puzzle