Glycoprotein Ibα Kozak polymorphism in patients presenting with early-onset acute coronary syndrome.

INTRODUCTION: Glycoprotein Ibα (GPIbα) receptor is the chief molecule responsible for initial platelet adhesion to the subendothelium. A thymidine to cytosine single nucleotide substitution at position -5 from the ATG start codon characterizes the Kozak sequence polymorphism. The Kozak sequence polymorphism may increase the surface expression of GPIbα and contribute to thrombogenesis. We evaluated the allele frequencies of GPIbα Kozak sequence polymorphism in the Turkish population and examined the relationship between GPIbα Kozak sequence polymorphism and early-onset acute coronary syndrome (ACS). MATERIAL AND METHODS: This study enrolled 200 patients (122 male, 78 female, mean age: 39 ±5 years) and 200 healthy control subjects (110 male, 90 female, 41 ±4 years). The patient group was composed of patients admitted to our coronary care unit with early-onset ACS and patients who attended to our cardiology outpatient clinic after hospital discharge with a diagnosis of early-onset ACS. RESULTS: Kozak polymorphism frequencies in patients and control subjects did not differ significantly (23% versus 22.5%, p = 0.812, respectively). In patients who presented with non-ST elevation myocardial infarction (NSTEMI), the frequency of GPIbα Kozak polymorphism was borderline significantly higher when compared with patients who presented with ST elevation myocardial infarction (STEMI) (35% vs. 20%, p = 0.05, respectively). Allele frequencies of T and C were calculated to be 0.873 and 0.128. CONCLUSIONS: Although the frequency of GPIbα Kozak polymorphism did not differ significantly in early-onset ACS patients versus control subjects, Kozak polymorphism frequency was borderline significantly higher in patients who presented with NSTEMI when compared to patients with STEMI.

Glycoprotein Ib-alpha Kozak polymorphism in ischemic stroke.

BACKGROUND: Recently, a T/C polymorphism in the Kozak sequence of glycoprotein Ib-alpha (GPIb-alpha) gene at position -5 from the initiator ATG codons, has been identified. The presence of -5C allele increases the surface expression of GPIb-IX-V complex in a gene dosage-dependent manner. It has been suggested that higher receptor levels might increase the adhesiveness of the platelets and confer risk for thrombosis. In this study, we aimed to investigate the association between GPIb-alpha Kozak polymorphism and ischemic stroke. METHODS: We prospectively and consecutively recruited 231 patients (118 women and 113 men; mean age: 65 ± 14.2 years) with first ever ischemic stroke admitted to Istanbul Faculty of Medicine Edip Aktin Stroke Unit between April 2007 and June 2009. Demographic features, risk factors, clinical, and etiological subtypes were analyzed. As the control group, 220 unrelated healthy subjects were included. RESULTS: We found that 156 patients had TT, 70 patients had TC, and 5 patients had CC genotype. At least one copy of C allele carriers were overrepresented in the ischemic stroke group (32.5%) compared with controls (23%) [odds ratio (OR): 0.61; 95% confidence interval (CI): 0.40-0.93; P = 0.03]. Among etiologic subtypes, the distribution of C allele carriers was the highest in patients with undetermined etiology (45%) and it was significantly higher than controls (OR: 0.36; 95% CI: 0.20-0.65; P = 0.0008). In other subtypes, there was no association with Kozak -5C allele. CONCLUSION: In conclusion, these encouraging preliminary results show that GPIb-alpha T/C polymorphism might increase the risk of ischemic stroke, especially in those with undetermined etiology.

Acute myocardial infarction in a patient with hemophilia A and factor V Leiden mutation.

Factor VIII:C, epsilon amino-caproic acid or tranexamic acid are prophylactic agents used in preventing hemorrhage pre-operatively in patients with hemophilia A. Although hemophilia A seems to be a factor that avoids the development of acute myocardial infarction (AMI) as it tends to be associated with increased bleeding, it should be kept in mind that prothrombotic agents used pre-operatively for prophylaxis may increase the risk for AMI in the presence of the factor V Leiden mutation. In this report, we discuss the development of AMI following the use of recombinant factor VIII and tranexamic acid for prophylaxis in a patient with known hemophilia before a tooth extraction in conjunction with the relevant literature.

Leukocytoclastic vasculitis due to thalidomide in multiple myeloma.

Thalidomide is successfully used in the treatment of multiple myeloma, leprosy and various autoimmune diseases due to its anti-angiogenic, immunomodulatory and anti-inflammatory effects. Thalidomide's most common side effects are constipation, neuropathy, fatigue, sedation, rash, tremor and peripheral edema. We achieved complete response with a 400 mg/day dose thalidomide therapy in a 58-year-old male patient diagnosed with relapsing refractory multiple myeloma. While continuing thalidomide for sustainable response, the therapy was terminated at the ninth month due to development of leukocytoclastic vasculitis. We describe the case and discuss the place of thalidomide in the treatment of multiple myeloma and the rare occurrence of leukocytoclastic vasculitis during thalidomide therapy in multiple myeloma, since only one such case has been reported in the literature thus far.

Genotoxicity and sister chromatid exchange in patients with myelodysplastic disorders.

In this study, we aimed to evaluate genotoxicity by sister chromatid exchange frequency in the peripheral lymphocytes of patients with myelodysplastic syndrome (MDS). The study population consisted of 16 patients (females/males:6/10; mean age: 61.68 +/- 13.08 years) diagnosed with "refractory anemia" according to FAB classification. The results were compared with an age- and sex-matched control group. The sister chromatid exchange frequency in the study group was found to be significantly higher than the control group (8.3 +/- 11 vs. 6.83 +/- 1.07, P=0.0046). We suggest that increased DNA damage, which is revealed by the increased sister chromatid exchange in the present study may play a role in the etiopathogenesis of MDS.