Sabri Batun

Familial Mediterranean fever gene mutations in the Southeastern region of Turkey and their phenotypical features

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. Several studies have focused on the differences between frequency of the mutations and their phenotypical manifestations. The aim of this study was to evaluate whether or not this phenotypical variation is associated with the existence of particular mutations. Twelve MEFV (Mediterranean fever) gene mutations were investigated in 119 patients suffering from FMF. Heterozygote M694V (21/119), heterozygote E148Q (21/119), homozygote M694V (17/119) and heterozygote V726A (12/119) mutations were the most common mutations. Patients were grouped according to the presence of the M694V mutation: group I was M694V/M694V, group II was M694V/others, and group III was other/other. Mean severity scores for the groups were 13.94 ± 4.10, 10.79 ± 3.01 and 8.31 ± 2.26, respectively. There were statistically significant differences between the mean severity scores of groups I and II (p = 0.029), groups I and III (p < 0.0001), and groups II and III (p < 0.0001). Diagnosis of amyloidosis was established in four (23%) patients of group I, and three (8%) patients of group II, but in none of the patients in group III. There was also a statistically significant difference between groups I and III (p = 0.046), but not between groups II and III (p = 0.083) and groups I and II (p = 0.317) in terms of amyloidosis development. In conclusion, we found a higher disease severity score and higher prevalence of amyloidosis in FMF patients who were M694V mutation carriers. Many ethnic groups live in Anatolia and more ethnic origin-based studies are needed to determine the real effect of these mutations on disease severity and amyloidosis.

Factor V Leiden and G20210A prothrombin mutations in patients with recurrent pregnancy loss: data from the southeast of Turkey

Factor V Leiden (FV-Leiden) and prothrombin gene mutations (FII G20210A) are well-established independent risk factors for thrombosis. In the recent years, many studies have suggested that these mutations are associated with an increased risk of recurrent pregnancy loss (RPL). We aimed to investigate the prevalence of these molecular defects in subjects with a history of early RPL. One hundred and fourteen women with three or more consecutive unexplained first-trimester miscarriages were compared to 185 parous women with uncomplicated pregnancies from the same ethnic origin. The presence of FV-Leiden and FII G20210A mutations was assessed by polymerase chain reaction analysis. Overall, 11 out of the 114 women with early RPL (9.6%) had either FV-Leiden or FII G20210A mutation, as compared with 16 out of the 185 women with normal pregnancies (8.6%; p = 0.756). The prevalence of FV-Leiden mutation was 7.9% (9/114) in patient group, compared with 7% (13/185) in control group (p = 0.780). One hundred and two patients were primary and 12 were secondary aborters. All FV-Leiden positive cases were primary aborters (8.8%; 9/102, p = 0.584). Concerning the FII G20210A, two out of 114 (1.7%) were first-trimester RPL (primary aborters) and three out of 185 (1.6%) controls were carriers of the FII G20210A mutation (1.7 vs 1.6%, p = 0.931). The results obtained from patients with first-trimester RPL and the control group have no statistical significant differences in the prevalence of FV-Leiden and FII G20210A mutations. These results suggest that mutations have no role in etiology of first-trimester recurrent abortions.

Effects of Extremely Low Frequency Electromagnetic Fields on Hematologic and Immunologic Parameters in Welders

BACKGROUND Electric arc welding is known to cause considerable exposure to extremely low frequency magnetic fields. Although some studies of exposure to magnetic fields and epidemiologic studies have included groups of welders, typically little information is available concerning the hematologic and immunologic effects of ELF electromagnetic fields on welders. Therefore, the aim of the present study is to investigate whether or not extremely low frequency electromagnetic fields (ELF EMF) emitted from electric arc welding affect some hematologic and immunologic parameters of welders. METHODS The study was carried out on 16 male welders and 14 healthy males between 20 and 40 years of age from the same geographic area and with similar life styles. The following hematologic and immunologic parameters were measured in both groups: red blood cells (RBC); hemoglobin (Hgb); hematocrit (Hct); platelets (Plt); total white blood cells (WBC); neutrophils; lymphocytes; eosinophils; and CD3, CD4, CD8, and CD4/CD8. RESULTS Some of the hematologic and immunologic parameters under investigation were similar in both groups. Although T lymphocyte surface antigens, such as levels of CD4 and CD8(,) were found to be lower in the welders than in the control subjects (p <0.001, p <0.05), the hematocrit levels of the welders were found to be higher than those of the control subjects (p <0.05). However, the differences observed were not clinically significant. ELF electromagnetic field intensities in the welding areas varied between 0.10 and 0.25 mT. CONCLUSIONS These results suggest that ELF electromagnetic fields do not affect the hematologic and immunologic parameters of welders.

A comprehensive analysis of 12 thrombophilic mutations and related parameters in patients with inflammatory bowel disease: data from Turkey

BackgroundPossible association of inflammatory bowel disease (IBD) with the most common inherited prothrombotic conditions has been the focus of many investigations. Advance in modern molecular biology is expanding the thrombophilia evaluation steadily. We tried to put forward a comprehensive thrombophilic profile in IBD and to see the probable role of this profile in pathogenesis.MethodsA total of 60 adults (33 patients and 27 healthy controls) were included. We used the CVD-StripAssay which is based on the reverse-hybridization principle to identify a total of 12 thrombophilic gene mutations: Factor V R506Q, Factor V H1299R, prothrombin G20210A, Factor XIII V34L, beta-Fibrinogen-455 G-A, PAI-1 4G/5G, platelet GPIIIa L33P, MTHFR C677T, MTHFR A1298C, ACE I/D, Apo B R3500Q and Apo E2/E3/E4, respectively. Besides, we evaluated many related blood parameters such as protein C, protein S, AT-III, IL-6, TNF-alpha, Apo-A1, Apo-B100, homocysteine (tHcy) etc. using commercially available assays.ResultsThe frequencies of genetic polymorphisms were found to be statistically insignificant among patients and controls, except for three: Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D. Two patients with a history of deep venous thrombosis had more than one polymorphism. Patients with MTHFR C677T and MTHFR A1298C gene mutations had a similar mean tHcy levels with controls. Patients with Apolipoprotein B R3500Q and Apolipoprotein E4 gene mutations had similar mean LDL-cholesterol levels. Mean total cholesterol and triglyceride levels were similar in patients and controls of Apo E2, E3, E4 alleles.ConclusionPredominantly, the presence of genetic mutations that predispose to hypercoagulable states does not appear to be in correlation with IBD. There was a statistical difference between the proportions of the mutated allele frequencies of Beta-Fibrinogen-455G-A, MTHFR A1298C and ACE-I/D in IBD.

Prevalence of antineutrophil cytoplasmic antibody positivity in patients with Hodgkin’s and non-Hodgkin lymphoma: a single center experience

Hematological malignancies are associated with the release of different autoantibodies and rheumatological manifestations. Systemic vasculitides are rare in hematological malignancies, and antineutrophil cytoplasmic antibodies (ANCA) have not been described sufficiently in hematological malignancies. In this present prospective study, we examined the prevalence of ANCA and related disease in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients in the southeast region of Turkey. We examined 119 patients with previously or newly diagnosed NHL and 60 patients with HL for the presence of ANCA and related autoimmune diseases between December 2002 and February 2007. ANCA positivity was detected in only 8 patients (4.4%); and all of these ANCA positivities were detected in patients in the HL group (13.3%); p-ANCA positivity was detected in 6 patients (3.3%); and c-ANCA positivity was detected in 2 patients (1.1%). There was statistically significant difference between patients with HL and NHL in terms of p-ANCA (p = 0.001) but none in c-ANCA (p = 0.111) positivity. None of the ANCA positive patients had vasculitides or rheumatic manifestations. In addition, we did not detect any ANCA positivity in the NHL group. In conclusion, ANCA positivities were detected only in HL patients; but we did not detect the association between ANCA positivities and rheumatic manifestations or vasculitis and also the different treatment responses in HL patients.

Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1000. The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world. Prothrombin G20210A (PT G20210A) gene mutation has been recently identified as a common risk factor in venous thrombosis. Sixty-one patients with VT, differing in age and sex, and 340 healthy subjects were consecutively enrolled into our study to determine the prevalence of PT G20210A in VT and in the healthy population of the southeast of Turkey. The mutation was identified with fluorescence resonance energy transfer (FRET) with the LightCycler polymerase chain reaction. The PT G20210A mutation was found to be 6.5% (4/61) in the VT group and 1.2% (4/340) in the healthy group (P = 0.021). Three patients with VT had a heterozygous PT G20210A mutation, and the other patient with VT had both Factor V Leiden and PT G20210A mutations. We showed that this method may be used safely for detection of the PT G20210A gene mutation, and the prevalence of PT G20210A mutation is significantly higher in patients with VT than in the healthy population in the southeast of Turkey.

Hepatitis C virus in patients with non-Hodgkin's lymphoma in southeastern Anatolia region of Turkey: A prospective case-control study of 119 patients

Hepatitis C virus (HCV) has been associated with several extrahepatic disorders including mixed cryoglobulinemia (MC), autoimmune thyroiditis, Sjogrens syndrome. Such associations have led to the suggestion that HCV may participate in the development of various immunmediated disorders. Recently, it has been hypothesised that HCV might act as a trigger for the development of monoclonal B-cell disorders such as non-Hodgkins lymphoma (NHL). Discordant data have been reported in different geographic regions of the world. The aim of this prospective case-control study was to detect the prevalence of HCV in patients with NHL in southeastern Anatolia region of Turkey. In this study, HCV antibody prevalence and cryoglobulinemia were investigated in 119 patients with histologically diagnosed NHL. The control group consisted of 117 patients who visited the outpatient clinic of internal medicine. None of the patients had HCV antibody positive (0%) with the enzyme immunoassay and reverse transcriptase polymerase chain reaction (RT-PCR). One of the control patients had positive HCV antibody (0.9%). Our data does not support the association between HCV infection and NHL in southeastern Anatolia region of Turkey.

Factor V Leiden mutation in venous thrombosis in southeast Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.

Molecular basis of beta-thalassemia mutations in Diyarbakir in the southeastern region of Turkey.

b-Thalassemia (thal) is a common single gene disorder; it has been estimated that 3% of the world’s population (150 million people) carry a thalassemic gene. b-Thalassemia is an autosomal recessive disease characterized by a hypochromic, hemolytic anemia and dependence on blood transfusions to sustain life (1). Heterozygote carriers are essentially normal. They can usually be detected by screening red cell indices, that demonstrate a reduced mean corpuscular hemoglobin (Hb) value, and an elevated Hb A2 level (1). b-Thalassemia has a high frequency in the Mediterranean Basin, Africa, India, Southeast Asia, Iran, and Turkey. This disease is the most common genetic disorder in Turkey. Molecular cloning and DNA sequencing led to the identification of several mutations responsible for defect in the gene function (2). In the Turkish population, Professor Nazli Basak and her colleagues (Bogazici University, Istanbul, Turkey) have characterized more than 18 different mutations (3–5). The six most frequent alleles, accounting for about 70% of the cases, are IVS-1-110 (G!A), IVS-I-6 (T!C), the frameshift at codon (FSC) 8 ( AA), IVS-I-1 (G!A), 30 (T!A), and FSC 5 ( CT). We report here the results of a molecular screening carried out in a population from the southeastern region of Turkey, a region with an unknown incidence of thalassemia, by

Hereditary Thrombophilic Factors in Stroke Due to Cerebral Infarct

Background:The stroke is the third most common cause of all deaths. In new studies, the importance of hereditary thrombophilic factors on stroke is emphasized. The aim of this study is to determine the role of hereditary thrombophilic factors including factor V Leiden A1691G (FVL), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations in patients with stroke because of cerebral infarct. Methods:Twenty-four patients with stroke and 53 controls with risk factor for stroke were enrolled. Polymerase chain reaction was used to detect these mutations. Results:Heterozygote FVL mutation in 2 (8.3%) patients and MTHFR mutation in 10 (41.7%) patients were detected. In the control group, there were 2 (3.8%) patients with heterozygote FVL mutation and 15 (28.3%) patients with MTHR mutation. Both FVL and MTHFR gene mutations were detected in 1 patient and 2 controls, respectively. Prothrombin gene mutation was not found in 2 groups. There were not statistically significant differences for all 3 mutations in-between 2 groups (P > 0.05). Odds ratios were 0.431 (0.074–2.504, 95% CI) for FVL mutation and 0.553 (0.221–1.381, 95% CI) for MTHFR mutation, respectively. Conclusion:Although our study group was small, hereditary thrombophilic factors might not be risk factors for stroke because of cerebral infarct.