The Role of Parkin in Rat Pancreatic Beta Cells Fate.

Parkin is a member of the mitochondrial quality control system that plays a major role in mitophagy. Although the loss of function mutations in the Parkin gene has been associated with the Familial Parkinson's phenotype, research in recent years points out that Parkin's function is not limited to neurodegenerative diseases. Parkin's function impressing key cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, makes it an important player in the maintenance of cellular homeostasis. In this study, we investigated whether Parkin affects cell viability and ER stress responses under lipotoxic conditions in INS-1E cells. Our results may suggest that silencing Parkin may affect autophagy in addition to apoptosis.  We also showed that Parkin may have a protective effect against lipo-toxic effects in INS-1E cells. Consistent with previous studies, we observed that stress responses were different for high and low palmitic acid doses. The Parkin being inhibited under high-dose PA treatment and active under low-dose PA treatment indicate that regulation of stress responses is controlled by environmental conditions. Our preliminary findings may suggest that in low lipotoxic conditions, Parkin affects the ER stress response by modulating Chop activity and Ca2+ release from the ER to the cytoplasm.

A Lipotoxic Medium Decreases the Number of Lipid Droplets in ß Cells: One Possible Explanation of the ß-Cell Failure in Patients With Hyperlipidemia Receiving Tacrolimus.

OBJECTIVES: Dyslipidemia is a risk factor for post- transplant diabetes mellitus, especially in patients who are taking tacrolimus. Although lipotoxicity of dyslipidemia leads to ß-cell failure, the handling of lipids by ß cells is a mystery in molecular endocrinology. Likewise, lipid droplet homeostasis is appreciated as a key component of lipid metabolism in cells like hepatocytes, but its role in ß cells remains to be elucidated. MATERIALS AND METHODS: To evaluate the morphologic changes in ß cells with special focus on lipid droplets, we evaluated electron micrographs under metabolic stress conditions of glucotoxicity, lipotoxicity, and glucolipotoxicity in isolated rat insulinoma INS-1E ß cells. Cells were treated with palmitic acid (0.5 mM), glucose (33 mM), or both for 16 hours, after which morphologic changes were observed with an electron microscope. RESULTS: Many lipid droplets were observed in the cytoplasm of healthy ß cells in the control group (no treatment). Lipid droplets were also visible in the cytosol, and the cytoplasm was rich in organelles and insulin vesicles under high glucose stimulation. However, after treatment with palmitic acid, almost no lipid droplets were observed. Endocrine vesicles were also depleted, with severe morphologic disruption of other organelles. Under glucolipotoxic conditions, ß cells showed a decreased number of lipid droplets and insulin vesicles compared with controls. CONCLUSIONS: Lipid droplet dynamics seemed important in the homeostasis of ß-cell metabolism. In this preliminary study, healthy ß cells appeared rich in lipid droplets under normal conditions. However, lipotoxicity depleted and glucolipotoxicity decreased the number of lipid droplets in ß cells. Because dyslipidemia causing lipotoxicity is one of the most frequent metabolic problems in transplant patients and increases risk of posttransplant diabetes mellitus, understanding the mystery of lipid droplets in ß cells and the pathophysiology of diabetes in transplant patients is important, especially for those taking tacrolimus.

Beta-Cell Golgi Stress Response to Lipotoxicity and Glucolipotoxicity: A Preliminary Study of a Potential Mechanism of Beta-Cell Failure in Posttransplant Diabetes and Intraportal Islet Transplant.

OBJECTIVES: Lipotoxicity and glucolipotoxicity are among the mostimportanttriggers of beta-cell failure in patients with type 2 and posttransplant diabetes. Because the Golgi apparatus is a vital organelle in secretory cells like beta cells, its behavior under stress conditions determines the cell's functional capacity. MATERIALS AND METHODS: To mimic lipotoxicity and glucolipotoxicity as metabolic stresses for beta-cell failure, rat insulinoma INS-1E cells were treated with palmitic acid, glucose, or both. Cells were cultured in the presence of 5.0, 16.7, or 33 mM glucose with or without 0.5 mM palmitic acid for 8, 16, 24, and 48 hours. Incubation in the presence of any of the 3 concentrations of glucose with 0.5 mM palmitic acid provided glucolipotoxicity. In addition to the endoplasmic reticulum stress marker (Hspa5), we evaluated changes in Golgi function under experimental metabolic stresses. In doing this, we measured expression levels of the genes coding Golgi structural proteins (Acbd3,Golga2, and Arf1), Golgi glycosylation enzymes sialyltransferaz10 and sialyltransferase 1 (St3gal1), and Golgi stress mediators (Creb3 and Arf4). RESULTS: Golgi responded to lipotoxicity and glucolipotoxicity by increasing the expression of St3gal1 (P = .05 in both conditions) and Creb3 (P = .022 and P = .01, respectively). The Arf4 gene transcript also increased in glucolipotoxic media (P = .03). Glucotoxicity alone did not induce a change in the transcript levels of Creb3 and Arf4. Lipotoxicity and glucolipotoxicity induced Creb3 and Arf4 expression, which are important Golgi stress response mediators leading to apoptosis. CONCLUSIONS: This preliminary study showed that the Golgi stress response is important in lipotoxic and glucolipotoxic conditions in terms of beta-cell failure. Solving the mystery of intracellular molecular mechanisms leading to beta-cell dysfunction is crucial to understanding the pathophysiology of posttransplant diabetes and most probably the failure of intraportal islet transplants in the long term.

Lack of association between MMP13 (rs3819089), ADAM12 (rs3740199-rs1871054) and ADAMTS14 (rs4747096) genotypes and advanced-stage knee osteoarthritis.

OBJECTIVES: The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). PATIENTS AND METHODS: A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the Kellgren-Lawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample. RESULTS: The most common nucleotides in both the control and patient groups were CG for rs3740199 and CT for rs1871054 in the ADAM12 gene, and the most common nucleotides in alleles were GG for MMP13 rs3819089 and AA for ADAMTS14 rs4747096. No statistically significant relationship was detected between the gene polymorphisms and advanced OA. CONCLUSION: The study results suggest that ADAM12 rs3740199 and rs1871054, MMP13 rs3819089, and ADAMTS14 rs4747096 polymorphisms have no relationship with knee OA susceptibility in the Turkish population. However, as this is the first study to investigate the relationship between the SNPs of ADAM12, ADAMTS14, and MMP13 genes and the development of OA in the Turkish population, it would contribute to our understanding of the molecular bases of OA.

Uncoupling protein gene UCP1-3826A/G, UCP2 Ins/Del and UCP3-55C/T polymorphisms in obese Turkish children.

BACKGROUND: Mitochondrial uncoupling proteins (UCP) 1, 2 and 3 are members of the anion carrier protein family located in the inner mitochondrial membrane. There are various controversial reports on UCP genotypes and obesity in adults and children. This study aims to investigate the link between mostly studied UCP polymorphisms (UCP1-3826A/G, UCP2 Insertion/Deletion (Ins/Del) polymorphism of exon 8, and UCP3-55C/T Polymorphisms) and obesity in Turkish children. Furthermore, the relationships of UCP polymorphisms are also analyzed within the scope of metabolic parameters of obese children. METHODS: Molecular screening of the UCP1, UCP2, and UCP3 gene polymorphisms was carried out in 189 children aged 6 to 18 years, 102 of who had exogenous obesity (54 girls) and 87 of whom were healthy controls (48 girls). In the obese group, fasting lipids, glucose and insulin levels were measured. In 60 obese children, an oral glucose tolerance test (OGTT) was performed with 0, 30, 60, 90 and 120 minutes of sampling for plasma glucose and insulin levels. RESULTS: The frequency of UCP polymorphisms was similar in obese and non-obese children. In obese children, fasting lipids, glucose and insulin levels were not different among the UCP 1, 2 and 3 genotypes. While no relationship was found between the UCP 1 and 3 genotypes and glucose/insulin levels during OGTT, carriers of the Insertion allele with UCP2 Ins/Del polymorphism had significantly higher 30-minute insulin levels (p=0.018). CONCLUSIONS: Polymorphisms of the UCP1-3826A/G, UCP2 Ins/Del, and UCP3-55C/T are not associated with obesity and related pathologies in Turkish children. However, the presence of the Ins allele of the UCP2 gene has been found to have an unfavorable influence on early insulin excursion after glucose loading.

Effect of maternal and neonatal interleukin-6 - 174 G/C polymorphism on preterm birth and neonatal morbidity.

OBJECTIVE: The aim of this study was to analyze maternal and neonatal interleukin 6 (IL-6) (-174 G/C) polymorphism and to determine effect on preterm birth and neonatal morbidity. STUDY DESIGN: One hundred and sixty-four mothers (100 term births, 64 preterm births) and 183 newborn infants who were 100 healthy term and 83 preterm babies followed in newborn intensive care units were evaluated. PCR-RFLP was performed for IL-6 (-174 G/C) genotyping. RESULTS: The rate of GG genotype in mothers of term and preterm infants were 54% (n = 54/100), 75% (n = 48/64), respectively (p > .05) and the rate of GC + CC genotype was 46% (n = 46/100) and 25% (n = 16/64) in mothers giving term and preterm birth (PTB), respectively (p < .05). Additionally, the rate of GG genotype was 65% (n = 65/100) and 81.9% (n = 68/83) in term infants and preterm infants, respectively. GC + CC genotype was 35% (n = 35/100) in term infants and 18.1% (n = 15/83) in preterm infants (p < .05). The effect of IL-6 (-174) GC + CC genotype on PTB was statistically significant. CONCLUSION: The IL-6 174 G/C gene polymorphism was significantly different between mothers who were giving to term and preterm birth. The presence of polymorphism is protective against preterm birth and was not associated with neonatal outcome.

Endothelial nitric oxide synthase gene polymorphisms in patients with slow coronary flow.

BACKGROUND AND AIMS: The aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NO x ) concentrations and eNOS gene polymorphisms was also assessed. MATERIALS AND METHODS: The intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61). RESULTS: Plasma NO x level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NO x concentrations with respect to the relevant genotypes were found insignificant. DISCUSSION AND CONCLUSION: Plasma NO x is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.

Aspirin resistance in cerebrovascular disease and the role of glycoprotein IIIa polymorphism in Turkish stroke patients.

Aspirin resistance occurs in 5-45% of high-risk patients, with various mechanisms proposed for its development. This study aimed to determine the relationships among aspirin resistance, aspirin dosage, type of aspirin and glycoprotein IIIa P1A1/A2 polymorphism in patients with vascular risk factors. Two hundred and eight (75 symptomatic, 133 asymptomatic) patients with vascular risk factors who were using aspirin for primary or secondary prevention were prospectively included. The symptomatic group was further classified into two groups according to aspirin use at the time of stroke. Aspirin resistance was measured by the PFA-100 system (collagen/epinephrine cartridge) and glycoprotein IIIa P1A1/A2 polymorphism was determined by PCR. The overall prevalence of aspirin resistance was 32.2%. The mean age of patients with aspirin resistance was significantly higher than that in those who did not have resistance (P = 0.009). The prevalence of aspirin resistance was similar for the symptomatic and asymptomatic under aspirin therapy groups. The resistance rate was found to be highest with 100 mg enteric-coated preparation use (39.3%). Increasing the aspirin dosage and/or shifting to uncoated preparations caused a change in aspirin sensitivity of 36-60%. Repeated measurements showed development of aspirin resistance in 14% of patients who were sensitive to aspirin in previous measurements. Glycoprotein IIIaP1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke were not significantly related. The effect of aspirin can change by time, dosage and type of preparation used. There are no relationships among glycoprotein IIIa P1A1/A2 polymorphism, aspirin resistance and development of atherothrombotic stroke.

ß-3AR W64R Polymorphism and 30-Minute Post-Challenge Plasma Glucose Levels in Obese Children.

OBJECTIVE: In this study, we aimed to investigate the association of W64R polymorphism of the ß3-adrenergic receptor gene (ß-3AR) with childhood obesity and related pathologies. METHODS: ß-3AR gene W64R genotyping was carried out in 251 children aged 6-18 years. Of these subjects, 130 were obese (62 boys) and 121 were normal-weight (53 boys). In the obese group, fasting lipids, glucose and insulin levels were measured. Oral glucose tolerance test (OGTT) was performed in 75 of the obese patients. RESULTS: The frequency of W64R genotype was similar in obese and non-obese children. In obese children, relative body mass index, waist-to-hip ratio, serum lipid, glucose and insulin levels, as well as homeostasis model assessment of insulin resistance (HOMA-IR) scores were not different between Arg allele carriers (W64R and R64R) and noncarriers (W64W). In 75 obese children, OGTT results showed that Arg allele carriers had significantly higher 30-minute glucose levels (p=0.027). CONCLUSION: W64R polymorphism of the ß-3AR gene is not associated with obesity and waist-to-hip ratio in Turkish children. Although there were no relationships between the genotypes and lipid, glucose/insulin levels or HOMA-IR, the presence of W64R variant seemed to have an unfavorable influence on early glucose excursion after glucose loading.

Involvement of Toll-like receptors in cervical cancer susceptibility among Tunisian women.

Previous studies underscored the importance of genetic factors in the pathogenesis of certain cancers, including cervical cancer. Epidemiological evidence supports an association between specific polymorphisms of Toll-like receptors (TLR) with several human pathological states, including cervical cancer. The aim of this study was to investigate the link between specific gene variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study subjects comprised 122 women with histopathologically-confirmed cervical cancer, and 260 unrelated age- and ethnically-matched healthy females, who served as controls. TLR genotyping was done using PCR-restriction fragment length polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the Asp/Asp genotype and the Asp allele were associated with higher risk of developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11-13.50) respectively. We demonstrated no association between the TLR2 (-196 to -174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of cervical cancer among Tunisian women. However, the C/C genotype for the TLR3 (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of cervical cancer.

Multidrug resistance 1 (MDR1) 3435C/T genotyping in childhood drug-resistant epilepsy.

INTRODUCTION: A mutation at nucleotide position 3435 in exon 26 of the multidrug resistance 1 (MDR1) gene is the most frequently studied polymorphism in relation to multidrug resistance. However, there are conflicting data as to whether the CC or TT genotype of the 3435C>T polymorphism is associated with drug resistance. METHODS AND RESULTS: We investigated the association between this polymorphism in drug-resistant childhood epilepsy by comparison with drug-responsive patients. In total, 59 patients with drug-resistant epilepsy, defined as having four or more seizures within a 12-month period while using three or more AEDs, 60 children with drug-responsive epilepsy who had remained seizure-free for 12months on their current AED regimen and 76 healthy children were involved in this study. Genotype frequencies in drug-resistant patients were as follows: 32.2% CC, 44.1% CT, 23.7% TT; in the drug-responsive group: 20.0% CC, 50.0% CT, 30.0% TT; in the control group: 24.3% CC, 50.0% CT, 25.7% TT. Comparison of drug-resistant and drug-responsive patients revealed no significant difference in genotype frequency. The findings of the epilepsy patients were not significantly different from those of the healthy control subjects. CONCLUSIONS: Our study does not support any significant association between the MDR1 polymorphism and drug-resistant childhood epilepsy.

Associations between endothelial nitric oxide synthase A/B, angiotensin converting enzyme I/D and serotonin transporter L/S gene polymorphisms with pulmonary hypertension in COPD patients.

Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (p = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships.

[Associations between TGF-ß1 G/A and TNF-α 308 G/A gene polymorphisms with airway resistance in chronic obstructive pulmonary disease]. / Kronik obstrüktif akciger hastaliginda TGF-ß1 G/A ve TNF-α 308 G/A gen polimorfizmleri ile hava yolu direncinin degerlendirilmesi.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an important morbidity and mortality cause all over the world. Although specific gene region has not been defined in the pathogenesis of COPD, cytokine gene polymorphisms like tumor necrosis factor-alfa (TNF-α) and transforming growth factor-beta1 (TGF-ß1) may contribute to the development of COPD. The aim of the present study was to evaluate the associations between airway resistance with TGF-ß1 G/A and TNF-α 308 G/A gene polymorphisms in COPD patients. PATIENTS AND METHODS: 264 subjects were included to the study (Group 1; 75 COPD patients, Group 2; 139 subjects with at least 10 packet year smoking history without airflow obstruction, Group 3; 50 healthy subjects). Pulmonary function tests and body plethysmography to measure airway resistance were performed to the subjects. TGF-ß1 800 G/A and TNF-α 308 G/A gene polymorphisms were evaluated. Chi-square, Anova and correlation analysis were used for statistical analysis. RESULTS: There were significant difference among COPD stages in terms of TNF-α 308 G/A polymorphism (p< 0.05). Thirteen (23.6%) stage 1 COPD patients had TNF-α 308 G/A polymorphism and the other did not have. We did not find statistically significant difference among COPD stages in terms of TGF-ß1 800 G/A polymorphism (p> 0.05). TNF-α and TGF-ß1 genotypes and TNF-a 308 G/A and TGF-ß1 800 G/A polymorphisms were not different among study groups. Moreover, no significant differences betweeen subjects with and without increased airway resistance in terms of TNF-α 308 G/A and TGF-ß1 800 G/A polymorphisms were present. CONCLUSION: These results can suggest the lack of association between TNF-α 308 G/A and TGF-ß1 800 G/A gene polymorphisms with COPD development and airway resistance in Turkish population.

Atypical phenotypes of DYT1 dystonia in three children.

UNLABELLED: DYT-1 dystonia is the most common primary dystonia seen in childhood. It is an autosomal dominantly inherited disorder caused by deletion of a GAG triplet in exon 5 of the DYT1 gene. It characteristically starts in a distal limb during late childhood, subsequently spreads to involve other body regions sparing oromandibular muscles. However, clinical presentation can vary remarkably with respect to age, site of onset and progression. In this study we present three early-onset DYT-1 dystonia patients who are atypical according to age of onset and localization. Dystonia has started at 2, 3 and 7years of age and generalized to involve other limbs in all patients and also oromandibular muscles in one patient. None of them have benefited from medical treatments including L-dopa. All had normal brain MRI scan, a history of normal birth without significant perinatal asphyxia, infection or trauma and all are neurodevelopmentally otherwise normal. CONCLUSION: In children with dystonia; if brain imaging is unremarkable and when there is no history of CNS disorders such as perinatal asphyxia, infections, drug exposure or trauma; genetic analysis for GAG deletion of DYT-1 gene may be performed even if dystonia starts at a very young age or it spreads to involve oromandibular muscles.

Maternal-fetal proinflammatory cytokine gene polymorphism and preterm birth.

Association between maternal-fetal proinflammatory cytokine genotype and preterm birth was studied. Isolated genomic DNA from maternal and cord blood samples of 100 preterm and 101 term labors were used for TNFα (-238G/A, -308G/A), IL-1α (4845G/T), and IL-1ß (-511C/T) genotyping. TNFα -238 GA genotype in term neonates was significantly higher than the premature neonates (p<0.05). Maternal-fetal TNFα -238 heterozygosity was associated with term labor (p<0.05). TNFα -308 GA and AA genotypes were associated with term labor (mothers and neonates, respectively; p<0.05 and p<0.001). The incidence of term labor was significantly increased in TNFα -308 GA genotype. If a -308GA carrier has a fetus with GG genotype, the incidence of preterm labor increases (p<0.01). The 4845 T allele was significantly higher in preterm mothers and neonates (p<0.001 and p<0.001). The effect of maternal-fetal genotype for the pregnancy outcome reveals that maternal 4845GG and GT genotypes increase term labor incidence, whereas fetal 4845 TT genotype was a significant independent risk factor for preterm birth (p<0.01). IL-1ß -511 TT genotype was significantly higher in preterm neonates. The preterm labor risk was significantly increased in maternal -511 TT genotype and fetal CT genotypes, whereas with maternal -511 CT or TT genotypes or a -511 TT fetus, the incidence of term pregnancy increases (p<0.01).

Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis.

Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients (P = .04) with allele frequency of 6.3% (P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients (P = .001) with allele frequency of 6.9% (P = .003). MTHFR 677TT genotype was significantly higher in patients (P = .009) with allele frequency of 23.8% (P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies (P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.

Transforming growth factor-beta1 (509 C/T, 915 G/C, 869 T/C) polymorphisms are not related to obesity in Turkish children.

Increasing expression of transforming growth factor-beta 1 (TGF-beta1) from fatty tissue affects the serum level and hence may stimulate expression of the other cytokines. The studies concerning the relation between TGF-beta1 polymorphisms and obesity have been performed in adults, and diverse results have been reported. In this study, we aimed to investigate the association of TGF-beta1 509 C/T, 915 G/C, 869 T/C polymorphisms in childhood obesity and related pathologies. Two hundred and seventy-one children and adolescents were included in the study. One hundred and twenty-one of these cases were in the Obese Group and 150 were in the Control Group. In the Obesity Group, we searched the carbohydrate and lipid metabolism disorders such as insulin resistance, dyslipidemia and hepatosteatosis. The results of this study revealed the lack of an association between TGF-beta1 509 C/T, 915 G/C and 869 T/C polymorphisms and obesity. There were no relations between the polymorphism genotypes and obesity-related metabolic disturbances.

Lack of association between FXIII-Val34Leu, FVII-323 del/ins, and transforming growth factor beta1 (915G/T) gene polymorphisms and bronchopulmonary dysplasia: a single-center study.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease of preterm infants that is characterized by airway injury, inflammation, and parenchymal remodeling. Extravascular fibrin deposits in septae and alveoli due to the altered fibrin turnover are the pathological hallmarks of BPD that strongly indicates the importance of the imbalance in the competing activities of coagulation and fibrinolysis. Activation of the coagulation cascade leads to intraalveolar fibrin deposition in many inflammatory pulmonary disorders. Increased fibrin formation or decreased fibrinolysis may cause extravascular fibrin deposition. We evaluated the association between FXIII-Val34Leu, FVII-323 del/ins, and transforming growth factor beta1 (TGF-beta(1)) (915G/T) gene polymorphisms in patients with BPD. The study group consisted of 98 preterm infants with BPD. Ninety-four of the 192 preterm neonates were without BPD and sampled for the control group. Restriction fragment size analyses were performed by examining digested PCR products for FXIII-Val34Leu, FVII-323 del/ins, and TGF-beta(1) (915G/C) genotypes. No significant associations were found between FXIII-Val34Leu, FVII-323 del/ins, TGF-beta(1) (915G/C) gene polymorphisms and BPD phenotype in our population. Further studies with other genes are required for the identification of molecular predisposing factors for BPD that may help in the development of new treatments and hence might allow for targeting of this treatment to a "high-risk" subgroup, reducing unnecessary exposure to potentially harmful therapies.

Cardiac transplant in a child with recurrent thrombosis due to congenital thrombophilic mutations.

A modified Blalock-Taussig shunt had been implanted 3 times to treat cyanosis to a patient who has uncorrectable congenital cardiac deformity. We repaired the entire pulmonary artery, from one hilus to the other, to prevent future stenosis while making cardiac transplant. Our patient was also heterozygous for 2 thrombophilic mutations: methylene tetrahydrofolate reductase C677T and Factor V A4070G. Congenital risk factors should be evaluated in patients who have experienced a thromboembolic event before cardiac surgery.

Prevalence of thrombophilic mutations and ACE I/D polymorphism in Turkish ischemic stroke patients.

The aim of this study was to evaluate the prevalence of factor V Leiden (FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations, and angiotensin-converting enzyme (ACE) I/D polymorphism in ischemic stroke (IS) patients. A total of 162 Turkish IS patients were included and analyzed according to stroke subtype by the TOAST classification. Their genotype data were compared with those of the control group, representing the healthy population, using the chi(2) test. The frequency of FVL heterozygocity was 12.3% in this series-higher than that in the normal population (9.8%; statistically insignificant, P = .478). The frequency of the ACE D/D genotype in all stroke patients and those with stroke of undetermined etiology was higher than that in our population (52.5% and 59.2%, respectively, vs 39.3%; statistically significant, P = .034, P = .020). Our results may suggest that ACE D/D genotype is a risk factor for IS, particularly in those with stroke of undetermined etiology in the Turkish population.