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.

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.

Investigation of the Relationship Between BK Virus and Human Leukocyte Antigens in Kidney Transplant Recipients.

OBJECTIVES: The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been found to be related to HLA molecules. In renal transplant, the main target of the recipient's immune system is the HLA molecules on the surface of donor cells. HLA also plays a role in the development of an immune response to viral infections. After renal transplant, BK virus infections may occur due to immunosuppression. Here, we investigated the relationship between HLA and BK virus in renal transplant recipients. MATERIALS AND METHODS: This retrospective study investigated HLA-A, HLA-B, and HLA-DR tissue typing before renal transplant. DNA was isolated from whole blood, and tissue typing tests were performed based on polymerase chain reaction. Patients were tested for BK virus posttransplant using DNA isolated from urine and/or plasma samples. RESULTS: We found HLA-B*13 allele to be a protective factor (P < .049; odds ratio: 0.131; 95% confidence interval, 0.017-1.029) and HLA-DRB1*03 allele to be a possible risk factor (P < .029; odds ratio: 2.521; 95% confidence interval, 1.157-5.490) against BK virus. No significant relationships were found between BK virus and age, sex, donor type, and HLA mismatch. CONCLUSIONS: HLA class I molecules are known to be effective against viruses with the help of cytotoxic T cells. HLA-B*13 alleles within the HLA class I molecules were identified as protective factors against BK virus. HLA class II is associated with CD4-positive T cells that help secrete immune system cytokines, playing a role in stimulating and suppressing the immune system. We demonstrated that HLA-DRB1*03 allele could be a risk factor against BK virus. This allele may be associated with immunomodulatory cytokine secretion of the immune system.

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.

Angiotensin I-converting enzyme gene (I/D) polymorphism in patients with migraine.

In addition to the wide expression in many tissues including vascular endothelial cells, production of angiotensin II and degradation of bradykinin may indicate that angiotensin-converting enzyme could be involved in vascular tension and blood pressure. It has been reported that the deletion allele of the angiotensin-converting enzyme gene is associated with increased serum angiotensin-converting enzyme levels and linked to cerebrovascular diseases. In this study, the possible association of migraine with aura with the angiotensin-converting enzyme deletion-deletion (DD) and the angiotensin-converting enzyme insertion-deletion (ID) genotype was investigated in Turkish patients. To investigate the role of the angiotensin-converting enzyme I/D polymorphism in Turkish patients with migraine with aura, we analyzed the I/D genotype of 53 patients with that disorder. Twenty-two control subjects, who are volunteer Turkish patients without migraine, were included in the study. The frequency of the angiotensin-converting enzyme D/D genotype was statistically significant more frequent in patients with migraine with aura (81.1%) than in controls (59.1%) (P < .05). No differences were found regarding the I/I genotype and the I/D genotype between the 2 groups (P > .05). The results of our study revealed that the angiotensin-converting enzyme D/D genotype was more frequent in patients with migraine with aura than in controls. This might suggest that the angiotensin-converting enzyme D/D genotype may be a genetic risk factor for migraine with aura in Turkish patients.

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.

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.

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.

Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in Turkish children with asthma and allergic rhinitis.

Plasminogen activator inhibitor (PAI-1) has an essential role in tissue remodeling after inflammation. Recent literature revealed only one study evaluating PAI-1 4G/5G gene polymorphism in children with asthma and none in children with allergic rhinitis. We aimed to investigate distribution of PAI-1 4G/5G polymorphism in a group of Turkish children with asthma and allergic rhinitis and compare these findings with those obtained in normal peers. Patients with physician-diagnosed asthma (n = 106) and allergic rhinitis (n = 99) and 83 healthy peers were included in this study. We evaluated PAI-1 4G/5G polymorphism genotype as well as the possible association between PAI-1 4G/5G polymorphism and pulmonary function tests, serum total immunoglobulin E (IgE), total eosinophil count, and skin-prick test positivity in our study. The prevalence of the 4G allele significantly exceeded the values found in the controls both in patients with asthma (p = 0.001) and in patients with allergic rhinitis (p = 0.002). Interestingly, comparison of asthmatic patients revealed that mean baseline percent forced expiratory volume in 1 second and forced vital capacity were significantly higher in patients who bear 5G/5G genotype than in those who have 4G/4G or 4G/5G genotypes. No statistically significant relationship were found between PAI-1 polymorphism and total serum IgE levels, total eosinophil count, or selected skin test responses to aeroallergens. Our study suggests that Turkish children with asthma or allergic rhinitis have a higher prevalence of PAI-1 4G allele compared with their healthy peers.

Clinical importance of vitamin D receptor gene polymorphism in invasive ductal carcinoma.

In this study, we aimed to investigate the clinical importance of the vitamin D receptor gene polymorphism in invasive ductal breast cancer. All patients included in the study had clinical T1-2, N0-M0 invasive ductal carcinoma. Patients' demographics, axillary metastasis status, metastatic lymph nodi/total dissected lymph nodes from axilla, histopathologic characteristics of tumors, local recurrences, and survival ratio were assessed. Vitamin D receptor B genotype frequencies in the patient group (P > 0.05) were as follows: B/b, 43 (77%); B/B, 13 (23%). In conclusion, the vitamin D receptor gene B allele does not seem to be related to local recurrence and distant metastasis of invasive ductal cancer of the breast.

Thrombosis in children with cardiac pathology: analysis of acquired and inherited risk factors.

The present study was conducted to analyze the features and risk factors of childhood thrombotic events in patients with cardiac defect followed-up at our hospital. The clinical and laboratory findings of 59 patients diagnosed with cardiac defects and thromboses between 1997 and 2006 were retrospectively analyzed. Thirty-one children (52.5%) had venous system thromboses, 21 (35.6%) had arterial system thromboses, and seven (11.9%) had venous and arterial system thromboses. Presence of congenital heart disease and cardiomyopathy (CMP) were significant risk factors for developing intracardiac thrombosis. In addition, presence of congenital heart disease was the significant statistical risk factor for developing left atrium and right ventricle thromboses. Presence of congenital heart disease was a significant risk factor for developing a central nervous system thrombosis. Presence of pulmonary stenosis and aortic coarctation were significant risk factors for developing a peripheral arterial system thrombosis. Acquired risk factors including major surgery, angiography, central venous catheter, systemic infection, and hypoxia were identified in 49 of the 59 patients. Many patients had more than one of these acquired risk factors. Analysis of the relationship between thrombosis and type of major surgery demonstrated a statistically significant relationship between an intracardiac thrombosis and total correction of tetralogy of Fallot and a peripheral venous system thrombosis and a Blalock Taussig shunt. Twenty-three of the 52 patients (44.2%) had at least one thrombophilic mutation. Overall, a heterozygous factor V Leiden mutation was found in nine patients (17.3%), a methylenetetrahydrofolate reductase 677C-T mutation in 15 patients (28.8%), and a PT 20210G-A mutation in three patients (5.8%). Our data suggest that cardiac defects are common risk factors for developing a childhood thrombosis. The type of disorder determines the site of thrombosis. Acquired risk factors may contribute to the development of a thrombosis. The results of this study also indicate that to ensure early diagnosis, routine screening for thrombosis should be performed in patients with a cardiac defect and that screening for factor V Leiden and PT 20210G-A mutations and other genetic risk factors should be included when assessing all patients with cardiac defects who present with a thrombosis, whether or not a predisposing factor has been identified.

PAI-1 gene 4G/5G polymorphism, cytokine levels and their relations with metabolic parameters in obese children.

Obesity is associated with the changes of plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor-alpha (TNFalpha) and transforming growth factor beta (TGFbeta) levels. However, the precise effect of the 4G allele on obesity is still contradictory. Here, we aimed to elucidate the role of the 4G/5G polymorphism of the PAI-1 gene on the PAI-1 level and determine the associations between cytokines, glucose and lipid metabolism parameters in obese children. Thirty-nine obese children (mean age 11.4 +/- 3.3 years) and 38 age-matched healthy control group (mean age 10.3 +/- 3.5 years) were included in the study. In all cases, serum levels of glucose, lipid and insulin were measured, homeostasis model assessment of insulin resistance (HOMA-IR) was calculated, and 4G/5G polymorphism of PAI-1 gene, plasma PAI-1 level and serum TNFalpha and TGFbeta levels were studied. The mean relative body mass index (BMI) and HOMA-IR score, VLDL, TG, insulin, PAI-1, TNFalpha levels were higher, and HDL and TGFbeta levels were lower in the obese group. The frequency of the 4G/4G genotype was considerably higher in obese children than in controls. Also, a positive correlation was found between PAI-1 and TNFalpha levels, and relative BMI, HOMA-IR score, insulin, TG, HDL levels. TGFbeta was inversely correlated only with relative BMI. There was no correlation among three cytokines. In conclusion, childhood obesity contributes to higher PAI-1 and TNFalpha and lower TGFbeta levels. Especially PAI-1 and TNFalpha accompany insulin resistance and dyslipidemia.

Proinflammatory cytokine single nucleotide polymorphisms in nasal polyposis.

OBJECTIVE: To investigate the association between nasal polyposis (NP) and single nucleotide polymorphisms of the proinflammatory cytokines IL (interleukin) 1alpha (the IL1A gene), IL-1beta (the IL1B gene), and tumor necrosis factor alpha (the TNFA gene). DESIGN: Prospective case-control trial. SETTING: Tertiary referral center. PATIENTS: Eighty-two patients with NP and 106 healthy volunteers without sinonasal disease. MAIN OUTCOME MEASURES: Genotypes of IL1A (4845G, 4845T), IL1B (-511C, -511T) and TNFA (-238G, -238A and -308G, -308A) were identified by restriction fragment length polymorphism analyses after polymerase chain reaction. RESULTS: The 4845 GT and 4845 TT genotypes of the IL1A gene were associated with NP (P<.05). The frequency of the -511 CC genotype of the IL1B gene was significantly higher in patients with NP than in controls (P=.01). The frequency of the -511 CT genotype of IL1B was significantly higher (P=.01) in the controls than in the patients with NP. The -238 AA genotype of the TNFA gene was higher in the patients with NP than in the controls (P=.05). There was a significantly high risk of susceptibility to NP in patients with the -308 GA genotype of TNFA (P=.001). None of the genotypes of the proinflammatory cytokines were related to sex, the presence of atopy, asthma, or aspirin intolerance (P>.05). CONCLUSION: The IL1A (4845 GT and 4845 TT), IL1B (-511 CC), and TNFA (-238 AA and -308 GA) genotypes were associated with susceptibility to NP in our study population.

Endothelial nitric oxide synthase gene intron 4 (VNTR) polymorphism and vascular access graft thrombosis.

Vascular access thrombosis is a leading cause of vascular access failure in hemodialysis patients. Thrombosis is a multifactorial condition and genetic makeup can affect thrombosis risk. We conducted a study to investigate for possible associations between ecNOS gene intron 4 variable-number tandem repeat (VNTR) polymorphism and thrombosis of polytetrafluoroethylene hemodialysis arteriovenous access grafts (AVG) in Turkish patients. Fifty-five patients with end-stage renal disease who had AVGs implanted between 2000 and 2002 and 167 healthy individuals representing our healthy population were enrolled in this prospective study. Each subject provided a venous blood sample from which DNA was isolated, and polymerase chain reaction analysis was done to identify genotypes (aa, bb, ab) for ecNOS gene intron 4 VNTR polymorphism. All grafts were placed in brachioaxillary position. The subjects were divided into two groups based on duration of graft patency. The thrombosis group (Group I) comprised 26 patients who developed AVG thrombosis in the first 12 months after placement. The no-thrombosis group (Group II) comprised 29 patients whose grafts remained patient for at least 12 months. The frequency of the aa genotype in Group I was significantly higher than that in Group II (p = .005). At 6, 12, and 24 months, the primary patency rates for the AVGs in patients with the aa genotype were significantly lower than the corresponding rates for the bb and ab genotype groupings (p = .01, p = .01 and p = .04 for the three respective time points; Kaplan-Meier). ecNOS gene intron 4 VNTR polymorphism is linked with the pathogenesis of vascular access thrombosis in Turkish patients undergoing hemodialysis.

Methylenetetrahydrofolate reductase C677T mutation and nonalcoholic fatty liver disease.

A mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is known as one of the causes of hyperhomocyteinemia. The oxidation products of homocysteine can initiate lipid peroxidation, which has a central role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to assess the possible role of the MTHFR C677T mutation in the progression of simple steatosis to an advanced form of NAFLD. Thirty-four patients with NAFLD diagnosed by histologic analysis and 282 healthy controls were included in the study. The discrimination of nonalcoholic steatohepatitis (NASH) from another NAFLD was made by NAFLD activity score (NAS), and a NAS>or=5 was considered NASH. Patients with either NASH or nonalcoholic fatty liver (NAFL) and controls were evaluated for frequency of the MTHFR C677T mutation. The frequency of the MTHFR C677T mutation was 53.5% (CT, 44.7%; TT, 8.9%) in controls and 41.5% (CT, 37.7%; TT, 3.8%) in patients (odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34-1.12). There was no statistical difference in the frequency of this genotype between patients with NAFL and those with NASH (36% [CT, 28%; TT, 8%] vs 46.4% [CT, 46.4; TT, 0%]; OR, 0.65; 95% CI, 0.22-1.96). According to this study, the MTHFR C677T mutation does not seem to be a risk factor for the progression of NAFL to NASH.

Heterozygous methylenetetrahydrofolate reductase 677C-T gene mutation with mild hyperhomocysteinemia associated with intrauterine iliofemoral artery thrombosis.

Neonatal thrombosis is a serious event that can cause mortality or severe morbidity. Newborn-related factors, including genetic prothrombotic risk factors, may affect the occurrence of neonatal thrombosis. In this report, a case of intrauterine iliofemoral arterial thrombosis associated with mild hyperhomocysteinemia caused by methylenetetrahydrofolate reductase 677C-T gene mutation is presented. We suggest that methylenetetrahydrofolate reductase gene mutation might be investigated in neonates and their families presenting with thromboembolic disease.

The effect of plasminogen activator inhibitor-1 gene 4G/5G polymorphism on glucose and lipid metabolisms in Turkish obese children.

OBJECTIVE: Obesity is a metabolic disorder that is associated with increased plasminogen activator inhibitor-1 (PAI-1) concentration in the circulation. This increase is related to insulin resistance, dyslipidaemia and cardiovascular disease. Some studies have demonstrated a relationship between plasma PAI-1 concentrations and the 4G/5G gene polymorphism in the PAI-1 gene, while other studies have not. It is well known that plasma PAI-1 levels are increased in obesity; however, the relationship between the polymorphism and obesity remains unclear. In this study, we aimed to elucidate the effect of the PAI-1 4G/5G polymorphism on glucose and lipid metabolism parameters in Turkish obese children. DESIGN AND PATIENTS: Ninety children with obesity (37 male, 53 female; mean age 11.1 +/- 3.4 years; range 5.8-17.6 years) were included in the study. The children were divided into three groups according to the PAI-1 promoter 4G/5G polymorphism (4G/4G, 4G/5G and 5G/5G). These groups were compared for age, body mass index (BMI), serum glucose, lipid and insulin levels, and homeostasis model assessment of insulin resistance (HOMA-IR) score. RESULTS: The genotype distribution was 52% (47/90) 4G/4G, 25% (22/90) 4G/5G and 23% (21/90) 5G/5G. No statistically significant differences among genotype groups were found with respect to age, BMI, serum levels of glucose, lipid and insulin, and HOMA-IR score. CONCLUSION: Although the frequency of the 4G/4G genotype was higher in subjects in the current study than in subjects reported in the literature, in our study group we observed no influence of the PAI-1 4G/4G polymorphism on lipid and glucose metabolism.

Analysis of prothrombotic mutations and polymorphisms in children who developed thrombosis in the perioperative period of congenital cardiac surgery.

In this study, we investigated some of the prothrombothic mutations and polymorphisms in 15 children with congenital cardiac malformations who developed severe thrombosis in the perioperative period following surgical repair. The mutations and polymorphisms included in the study were Factor V Leiden, prothrombin G20210A, methylentetrahydrofolate reductase C677T, endothelial nitric oxide synthase intron 4 VNTR, alpha-fibrinogen Thr312Ala, Factor XIII Val34Leu, and insertion or deletion of angiotensin 1 converting enzyme. Compared to the healthy Turkish subjects, our patients had a similar rate of mutation of Factor V Leiden, Factor XIII Val34Leu, and endothelial nitric oxide synthase a/b polymorphisms, but higher frequency of the prothrombotic angiotensin 1 converting enzyme deletion/deletion genotype, and lower frequency of the antithrombotic alpha fibrinogen Thr/Thr genotype. None of the patients exhibited mutations involving prothrombin G20210A or methylentetrahydrofolate reductase C677T. The results of our study suggest that, in addition to prothrombotic mutations such as Factor V Leiden, single-nucleotide polymorphisms should be considered in all children with congenital cardiac malformations who develop thrombosis. Malformations of the heart are the most common of all serious lesions that are present at birth, with an incidence of 4 to 8 cases per 1,000 live births. If needed, corrective surgery is usually the optimal treatment for these anomalies, but perioperative morbidity and mortality still remain high due to several factors. Arterial or venous thrombosis, or both varieties of thrombosis, is among these factors. Prior to surgery, the most frequent time at which these children develop thrombosis is during cardiac catheterization. Postoperative thrombosis in this group of patients is a more complex disorder, which can affect both small and large vessels, and is associated with a high morbidity and mortality. Recent studies indicate that both point mutations and single-nucleotide polymorphisms of genes that encode proteins involved in the coagulative and anticoagulative cascades are important risk factors for development of thrombosis. Patients with these risk factors are most likely to develop thrombosis when triggering elements, such as placement of catheters, prolonged immobilization, or surgery, are also present. In this study, we investigated some of the above-mentioned mutations and polymorphisms in children who developed thrombosis in the perioperative period after correction of congenital cardiac malformations.