The drug-transporter gene MDR1 C3435T and G2677T/A polymorphisms and the risk of multidrug-resistant epilepsy in Turkish children

One-third of all individuals with epilepsy are resistant to antiepileptic drug (AED) treatment. Antiepileptic treatment response has been suggested to be modulated by genetic polymorphisms of drug efflux transporters. Several polymorphic variants within the multidrug resistance 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein, have been proposed to be associated with AED resistance in epilepsy patients. The aim of this study was to evaluate the effect of C3435T and G2677T/A polymorphisms of MDR1 on AED resistance in Turkish children with epilepsy. MDR1 C3435T and G2677T/A were genotyped in 152 patients with epilepsy, classified as drug-resistant in 69 and drug-responsive in 83. Genotypes of the C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction followed by restriction fragment length polymorphism. Genotype and allele frequencies of C3435T and G2677T/A polymorphisms of the MDR1 gene did not differ between drug-resistant and drug-responsive epilepsy patients. Our results suggest that MDR1 C3435T and G2677T/A polymorphisms are not associated with AED resistance in Turkish epileptic patients. To clarify the exact clinical implication of the MDR1 polymorphisms on the multidrug resistance in epilepsy, further investigations in various ethnic populations would be necessary

DNA repair gene XPD and XRCC1 polymorphisms and the risk of febrile neutropenia and mucositis in children with leukemia and lymphoma

The aim of the study is to investigate association between DNA repair gene XPD and XRCC1 polymorphisms and febrile neutropenia (FN) and mucositis. The study population consisted of 29 children with Burkitt lymphoma and 61 children with acute lymphoblastic leukemia. Analysis revealed that XRCC1194Trp allele showed a protective effect against longer FN and mucositis. There was also statistically increased risk for severe mucositis in patients with XRCC1Arg399Gln polymorphism. There are no studies that have examined this relationship before. Further studies with larger cohorts are needed to clarify the association. (C) 2011 Elsevier Ltd. All rights reserved

Association of the TLR4 and NOD2 Polymorphisms with Childhood Acute Lymphoblastic Leukemia

Objective: Immune activation plays a critical role in the immune response against cancer. Although several genetic factors are established with regard to the development of acute lymphoblastic leukemia (ALL), the role of immunogenic genes in ALL pathogenesis remains elusive. Toll-like receptor (TLR) and nucleotidebinding oligomerifation domain containing protein 2 (NOD2) receptors are essential in immune response. The aim of the study was to investigate the association between TLR4 Asp299Gly, TLR4 Thr399Ile, NOD2 Arg702Trp, NOD2 Gly908Arg, and NOD2 Leu1007fsinsC polymorphisms and the risk of childhood ALL

DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute lymphoblastic leukemia

Polymorphisms have been identified in several DNA repair genes. These polymorphisms may effect DNA repair capacity and modulate cancer Susceptibility. In this Study, we aimed to determine the fool polymorphisms in two DNA repair genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross-complementing group 1 (XRCC1). in a sample Of Turkish patients with childhood acute lymphoblastic leukemia (ALL), and evaluate their association with childhood ALL development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyze MID Asp312Asn, MID Lys75IGln, XRCC1 Arg194Trp. and XRCC1 Arg399Gln polymorphisnis in 70 patients with childhood ALL and in 75 disease-free controls, who were of a similar age. No significant differences were observed among the Study groups with regard to the MID codon 312, XPD codon 751. XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However, the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with increased risk for-ALL in females(OR=5.47: 95% CI= 1.49-20.10: p=0.008). This finding indicates that females carrying XRM 194Trp allele are at increased risk of developing childhood ALL. These results Suggest that the risk of childhood ALL may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing childhood ALL, and also should be lead to improved treatment of ALL. (C) 2008 Elsevier Ltd. All rights reserved

Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients

DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n = 20) with acute side effects and the control group (n = 20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P = 0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P = 0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P = 0.037) vs control (r = -0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer. (C) 2016 Elsevier B.V. All rights reserved

TNF-alpha 863C > A promoter and TNFRII 196T > G exonic variations may be risk factors for juvenile idiopathic arthritis

Background/aim: Juvenile idiopathic arthritis (JIA) is a chronic complex autoimmune disease. Genetic and environmental factors increase the risk of JIA. It is accepted that alterations in immune system pathways play an important role in the pathogenesis of JIA. The aim of the study was to investigate the possible association between immune system regulatory gene polymorphisms and JIA in Turkish patients

DNA repair gene XRCC1 polymorphisms and the risk of asthma in a Turkish population

Polymorphisms have been identified in several DNA damage repair genes. These polymorphisms may effect DNA repair capacity and modulate asthma susceptibility. In this study, we aimed to determine the two polymorphisms in DNA repair gene, x-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with asthma, and evaluate their association with asthma development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to analyze XRCC1 Arg194Trp and XRCC1 Arg399GIn polymorphisms in 116 patients with asthma and in 180 disease-free controls. Our data showed a positive association between the polymorphisms of codons 194 (odds ratio [OR] = 1.97, 95% confidence interval [CI] = 1.06-3.66, and p = 0.03 for Arg/Trp genotype) and 399 (OR = 1.87, 95% CI = 1.12-3.13, and p = 0.02 for Arg/Gln genotype, and OR = 2.59, 95% CI = 1.24-5.43, and p = 0.01 for Gln/Gln genotype) and asthma risk. No statistically significant difference was found for the allelic and genotypic distributions of the polymorphisms in XRCC1 gene between mild and moderate asthmatic patients. A combined analysis of the effect of XRCC1 codons 194 and 399 revealed the highest risk (OR = 4.17, 95% Cl = 1.77-9.83, and p = 0.001) for carriers of the polymorphic alleles in both of these codons. These results suggest that the risk of asthma may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing asthma and should lead to improved treatment of asthma. (Allergy Asthma Proc 31:349-354, 2010; doi: 10.2500/aap.2010.31.3332