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Genetic Polymorphisms Contribute to Acute Kidney Injury after Coronary Artery Bypass Grafting

BACKGROUND Acute kidney injury is one of the most serious complications after cardiac surgery. Genetic polymorphisms are reported to be associated with postoperative renal impairment. The aim of this study was to investigate the relationship between selected gene polymorphisms and acute kidney injury after cardiac surgery. METHODS Two hundred forty-eight elective coronary artery bypass grafting procedure patients were enrolled in the study. Angiotensin-converting enzyme (ACE) II, ID, and DD, apolipoprotein E (APO E), and angiotensin II type 1 receptor (AGTR1) A1166C genotypes were detected by polymerase chain reaction. Plasma levels of ACE were analyzed by enzyme-linked immunosorbent assay. Acute kidney injury after cardiac surgery was graded according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) classification. RESULTS In our study, 21.8% of patients had acute renal impairment after cardiac surgery. Among the 54 patients with acute kidney injury, ACE D allele frequency was 0.620. The plasma levels of ACE were significantly higher in the D allele carriers (P = .018). Three of the 54 patients with acute kidney injury were APO E epsilon 4 allele carriers (P = .002). AGTR1 C allele carriers constituted 46% of all patients with postoperative acute kidney injury. There was no statistically significant difference between A allele homozygotes and C allele carriers with respect to postoperative renal dysfunction (P > .05). CONCLUSIONS The present findings support the hypothesis that ACE I/D and APO E gene polymorphisms may play a role in the development of acute kidney injury after cardiac surgery. However, AGTR1 does not have a unique association with postoperative renal impairment.

Decreased IFN-γ and IL-12 levels in panic disorder

OBJECTIVE The aim of this study is to assess the measures of proinflammatory cytokines in patients with panic disorder in comparison with the healthy subjects. METHODS Twenty three patients with panic disorder with or without agoraphobia and twenty three controls were recruited for the study. Plasma samples of all subjects were analyzed for TNF-α, IFN-γ, IL-1β, IL-2, IL-6, and IL-12 concentrations and NK-cell activity is measured in the peripheral blood samples of the subjects. RESULTS We found significant differences on the mean values of IL-12 (p=0.01) and IFN-γ (p=0.02) between the panic disorder and control groups. In a logistic regression analysis, IFN-γ values were significant statistical predictors of the presence of panic disorder (B=-0.07, SE=0.03, p=0.04). CONCLUSION The most important implication of our results is to suggest a relation between panic disorder and low levels of IFN-γ, compatible with the results of the animal studies showing that IFN-γ plays a role by acting to regulate the development of anxiety-like behaviors.

Effects of myeloperoxidase −463 G/A gene polymorphism and plasma levels on coronary artery disease

Myeloperoxidase is a lysosomal enzyme of polymorphonuclear leucocytes that contributes to inflamatory responses. In previous studies it was shown that MPO was synthesized in atherosclerotic lesions responsible of lipoprotein oxidations. We aimed to determine the MPO −463 G/A gene polymorphism distribution in Turkish population and evaluate the effects of it on myeloperoxidase levels. There were 100 myocardial infarct patients and 100 healthy control subjects in our study. MPO polymorphism was studied by using PCR-RFLP technique and MPO levels were measured by ELISA. It was shown that MPO levels were increasing in patients after myocardial infarct event but there were no effect of MPO −463 G/A polymorphism on MPO levels. It was also found that serum total cholesterol and LDL-cholesterol levels and smoking was contributing factors in increments of MPO enzymes. We observed that MPO levels were increased in CAD but there were no effect of MPO −463 G/A polymorphism on MPO levels.

Manganese superoxide dismutase gene polymorphism, MnSOD plasma levels and risk of epithelial ovarian cancer

Aim:  We aimed to confirm any relation between the manganese‐containing superoxide dismutase (MnSOD) polymorphism and risk of ovarian carcinoma as well as to demonstrate any relation between the MnSOD mitochondrial signal sequence polymorphism and plasma MnSOD enzyme levels in women with ovarian carcinoma and healthy subjects.

The relationship of oral disturbances of diabetes mellitus patients with paraoxonase gene polymorphisms.

Diabetes Mellitus (DM) is a multisystemic disorder with serious complications and these patients may also have serious problems with their oral cavity probably because of the microangiopathic and neuropathic complications. In diabetic patients, there may be several problems of the oral cavity such as gingivitis, periodontitis, candidiasis, glossitis, oral ulcerations, loss of taste sensations, opportunistic infections and several other conditions dependent on these. One of the recent theories about complications in DM is the contribution of reactive oxygen radicals. Paraoxonase (PON1) is an enzyme that is synthesized in liver and having the capability of hydrolasing the active metabolite of an insectisid, parathion. Previously it was shown that there are two polymorphic areas on the PON1 gene: one causing a Leu → Met substitution at 55th position, the other causing Gln → Arg at the 192nd position. We investigated the differences in PON activities related to the oral lesions in Type 2 diabetics and control subjects to see their relationships with PON1 activity levels and the two main gene polymorphisms of PON1 genes, PON1 192 and PON1 55. We had 51 patients and 53 healthy subjects used in the study. PON activity was significantly decreased in Type 2 DM group compared to the control group. Neither PON1 192 nor PON1 55 genotypes had any differential effect on PON1 enzyme activity levels in either group. However, we found that PON1 55 M allele carriers had greater risk for general periodontal and/or gingival problems. Copyright

Neonatal hyperbilirubinemia and G71R mutation of the UGT1A1 gene in Turkish patients

Objective. Nonphysiologic hyperbilirubinemia of unexplained cause is prevalent among Turkish newborns, suggesting that there might be genetic risk factors in this population. Mutation of the UGT1A1 gene, glycine to arginine at codon 71 (G71R), is related to the development of neonatal jaundice in East Asian populations but the frequency of this mutation is rare among Caucasian populations. There are insufficient data on the G71R mutation in Turkish newborns with hyperbilirubinemia. The aim of this study was to investigate the genotypic distribution of the G71R mutation and its relationship with nonphysiologic hyperbilirubinemia of unexplained cause in Turkish newborns. Methods. Polymerase chain reaction, restriction fragment length polymorphism and agarose gel electrophoresis techniques were used for detection of G71R mutation in 109 newborn infants: 39 with hyperbilirubinemia and 70 without hyperbilirubinemia. Results. The genotypic distribution for the mutation was 70 G/G, 32 A/G, 7 A/A genotypes and the mutated allele frequency was 0.22. The frequency of G71R mutation was 33.3 % (n = 13) A/G, 7.7% (n = 3) A/A in the hyperbilirubinemia group and 27.1% (n = 19) A/R, 5% (n = 4) A/A in the nonhyperbilirubinemia group. The difference between the groups was not statistically significant. Conclusions. Our results suggest that G71R mutation of UGT1A1 is not rare; however, an association between G71R mutation and hyperbilirubinemia of unexplained cause has not been shown in Turkish newborns.

Paraoxonase 1 192 and 55 polymorphisms in nephrotic children

Human paraoxonase 1 (PON1) is a serum enzyme related to high-density lipoprotein which has a major role in preventing oxidative modification of low-density lipoprotein. Due to its amino acid substitution PON1 has two genetic polymorphisms. These polymorphisms are characterized by the location of glutamine (A genotype) and arginine (B genotype) at position 192, and leucine (L genotype) and methionine (M genotype) at position 55. Hyperlipidemia and increased lipid oxidation in nephrotic syndrome may lead to glomerulosclerosis and progression of the glomerular disease. In this study we aimed to investigate PON1 192 and PON1 55 polymorphisms in children with focal segmental glomerulosclerosis (FSGS) and control subjects. The study included 25 children with biopsy-proven FSGS and 30 healthy controls. We demonstrated a statistically significant difference between FSGS patients and control subjects with respect to the distribution of the PON1 polymorphism. The AA genotype was less frequent and the AB+BB genotype was more frequent in FSGS patients than in controls (48 versus 73% for AA genotype and 52 versus 27% for AB+BB genotype, p<0.05). Distributions of PON1 55 genotypes of FSGS and control subjects were also statistically different (76 versus 43% for LL genotype and 24 versus 57% for LM+MM genotype, p<0.05) (case-control study, dominant model, Fisher’s exact test). The distributions of both genotypes in subgroups of FSGS (stable renal function versus declining renal function) were not statistically different. We conclude in this preliminary study that presence of B allele and/or L allele may be risk factors for the development of FSGS in children.

Association between Laryngeal Squamous Cell Carcinoma and Polymorphisms in Tumor Necrosis Factor Related Apoptosis Induce Ligand (TRAIL), TRAIL Receptor and sTRAIL Levels

The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population.

Methylenetetrahydrofolate reductase C677T polymorphism in patients with Henoch-Schönlein purpura

Aim:  Associations between several vascular diseases such as Kawasaki disease, venous and arterial thromboembolism, cardiovascular disease, diabetic nephropathy, focal segmental glomerulosclerosis and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been reported. This is a clinical study designed to investigate the possible effects of MTHFR C677T polymorphism on the development of Henoch‐Schönlein purpura (HSP).

Association between FAS and FASL genetic variants and risk of primary brain tumor.

The purpose of this study was to investigate whether functional polymorphisms of apoptosis pathway genes FAS and FASL are associated with the development of primary brain tumors. The study constituted 83 patients with primary brain tumor and 108 healthy individuals. In the present case-control study, the primary brain tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS -1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm the genotyping, results were examined by DNA sequencing method. Our results were analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly lower in meningioma and glioma patients compared to controls (p = 0.023; p = 0.001, respectively). Multivariate logistic regression analysis revealed that FAS -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR = 0.092, 95% CI: 0.012–0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI: 0.007–0.428, p = 0.006 for gliomas). However, there was no significant differences in FASL -844 T/C genotype frequencies between patients with primary brain tumors and controls (p > 0.05). In this study, combined genotypes were evaluated for association with primary brain tumors. Combined genotype analysis showed that the frequencies of AATC and AACC were significantly lower in glioma patients in comparison with those of controls (p = 0.023; p = 0.022, respectively). This study provides the first evidence that FAS -1377 AA genotype may have a protective effect on the developing primary brain tumor in a Turkish population.