Nurcan Aras

The Association Between Polymorphic Genotypes of Glutathione S-Transferases and COPD in the Turkish Population

Although smoking is regarded as the most important causal factor in chronic obstructive pulmonary disease (COPD), only 10–20% of smokers develop symptomatic COPD, which indicates the presence of genetic predisposing factors in its pathogenesis. This study investigates the association between gene polymorphysims of glutathione S-transferases (GSTs) and COPD. Blood samples were taken from 149 patients and 150 healthy controls. Polymorphisms of GSTT1, GSTM1, and GSTP1 were genotyped using Real-Time PCR. Multivariate logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals between specific genotypes and COPD. There was no difference in the frequencies of the genotypes of GSTM1 and GSTT1 between the groups, but the GSTP1 Ile/Ile genotype was significantly higher in the patients than in the controls (61.1% vs. 38%). GSTP1 Ile/Val and Val/Val genotypes were associated with a decreased risk of COPD when compared to the Ile/Ile genotype (2.12-fold and 4-fold, respectively). Thus we suggest that the Val allele of GSTP1 may have a protective effect for development of COPD. Furthermore, when we evaluated the association between GSTP1 genes and smoking status, smokers with the GSTP1 Ile allele had an increased risk for the development of COPD. Among the combinations of the genotypes, the combination of GSTM1, GSTT1 null, and GSTP1 Val/Val was associated with the maximal increased risk (12-fold) of COPD. Thus to explain the ethiopathogenesis of COPD, investigation of a single gene family is inadequate. Based on our results and the previous data, further studies should be focused on the GSTP1 gene and the interactions with other genes such as polymorphisms of N-acetyltransferases, GSTM1 and GSTT1, microsomal epoxide hydrolase, and allelic variants of cytochrome P450.

TCF7L2 rs7903146 Gene Variation Is Associated with Risk of Type 2 Diabetes in Turkish Population

Type 2 diabetes (T2D) results from combination of environmental factors and genetic determinants. Transcription factor 7-like 2 (TCF7L2) genes have been reported that it plays important role in T2D pathogenesis. In addition, TCF7L2 gene polymorphisms have been linked to T2D through many European populations. In the present study, we investigated TCF7L2 polymorphisms in healthy individuals and T2D patients and aimed to see whether TCF7L2 polymorphisms are associated with T2D in the Turkish population. We genotyped two SNPs of TCF7L2 gene, rs7903146 and rs12255372 in 100 healthy individuals and 100 patients. As a result of the genotype and allele distributions, we found that there were significantly associations between the TCF7L2 rs7903146 and risk of T2D (p=0.0172) in Turkish Population. However, there was no association for TCF7L2 rs12255372 (p=0.395) but GT genotype was higher in patient groups (p=0.0250). Similarly, our data shows that individuals who carry TCF7L2 rs7903146 polymorphism have significant risk of T2D in Turkish population.

Glutathione S-transferase GSTM 1, null genotype may be associated with susceptibility to age-related cataract.

BACKGROUND Age-related cataract (ARC) is the leading cause of visual disability and reversible blindness all over the world. The different expressions of GST isozymes among animals may explain the variations in the cataract formation caused by oxidative stress. OBJECTIVES In this study, we evaluated the distribution of GST gene polymorphisms in ARC patients and the possible associations between the presence of ARC and GST gene polymorphisms. MATERIAL AND METHODS The epidemiological data was collected by a standard questionnaire and blood samples were obtained from 130 ARC patients and 159 healthy controls. Data about smoking habits of the groups was recorded. Real-time polymerase chain reaction-based methods were used to detect genetic polymorphisms. RESULTS The GSTM 1 null genotype was found to carry an increased risk for developing ARC (OR: 1.84, 95% CI: 1.13-2.99). The frequency of the GSTT 1 null genotype was not significantly different among the ARC patients and the controls (OR: 1.0, 95% CI: 0.64-1.6). The GSTP 1 Val/Val genotype was also not significantly different among the ARC patients and control groups (OR: 1.06, 95% CI: 0.50-2.23). GSTM 1 null genotype was highly frequent in non-smokers (OR: 3.25, 95% CI: 1.66-6.35) and moderately frequent in smokers (OR: 2.50, 95% CI: 1.28-4.86). Also, carrying the combined genotypes of GSTM 1 null, GSTT 1 and GSTP 1 105-Val allele was seen to have an increased risk of developing ARC (OR: 2.91, 95% CI: 1.31-6.44). CONCLUSIONS This data may provide evidence that GSTM 1 gene polymorphisms may be associated with genetic susceptibility to develop ARC. Larger studies are warranted to verify these findings.

Glutathione S-Transferase Z1 (GSTZ1) Gene Polymorphism in Gastric Cancer: A Preliminary Study in a Turkish Population

OBJECTIVE To determine whether there is a relationship between genetic polymorphisms of glutathione S-transferase zeta 1 (GSTZ1) and gastric cancer. The contribution of GSTZ1 genotypes to susceptibility to the risk of gastric cancer (GC) is still unclear. METHODS Using a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) method in an ethnic Turkish population, we examined the frequency of the GSTZ1 gene polymorphism in patients with GC patients (n = 73) and control individuals (n = 80). RESULTS For GSTZ1 A94G polymorphism, in the group of patients with the GC, the frequency of the GG genotype was quite a bit higher in comparison with that of the control group; however, this increase was not statistically significant. For the GSTZ1 A124G polymorphism, the GSTZ1 heterozygous genotype (AG) occurred more frequently in GC patients than in controls; however, it was not associated with risk of developing GC. We found no significant association between the A94G or A124G variants of the GSTZ1 gene and risk of gastric cancer. CONCLUSIONS Our data indicate no association between GSTZ1 genotypes and risk of gastric cancer. Despite its marked decline in many industrialized countries, gastric cancer remains the most common cause of death by cancer in areas such as Japan, Turkey, and South America. Gastric cancer (GC) is a disease of complex etiology that involves intimately interconnected infectious, dietary, environmental, and genetic factors. Although it has been estimated that 67% of GCs could be prevented by implementing lifestyle changes, the fact that some individuals develop GC but others do not, despite exposure to similar potentially carcinogenic factors, suggests that genetic predisposition may also play an important role in the etiology of GC.

1800 MHz radio-frequency electromagnetic radiation induces oxidative stress in rat liver, kidney and brain tissues

Mobile phone use has boomed out in recent years with an estimated 4.6 billion subscriptions globally. It has become an integral part of modern telecommunications. In many countries, over 50 % of the population uses mobile phones, and in some parts of the world, mobile phones are the most reliable or the only phones available. These gadgets use radiofrequency waves for transmitting data. The frequency band used for this varies from country to country (1). Generally the GSM (Global System for Mobile Communications) mobile phones use 900/1800 MHz frequency bands (2). Unlike ionizing radiation such as X-rays or gamma rays, radiofrequency fields can neither break chemical bonds nor cause ionization in the human body. Although this fact is true and well known to everyone, the interaction between this radiation and biological system is a major concern (3). The possible health effects of mobile phone radio-frequency electromagnetic radiation (RFEMR) are bothering the whole world because of the uncontrollable growth of the industry over the globe (4).

Apoptotic gene expression profiles and DNA damage levels in rat liver treated with perfluorooctane sulfonate and protective role of curcumin

Perfluorinated compounds (PFCs) such as PFOS and PFOA, are xenobiotics that can be detected worldwide in the environment and humans. PFOS (C8F17SO3-) is a fluorinated organic compound has been used for decades in industrial and commercial products. We investigated the genotoxic and apoptotic impact of PFOS in rat liver using comet assay, micronucleus test and apoptotic gene expression methods for caspase 3, caspase 8 and the protective role of curcumin on the PFOS- induced damage under chronic exposure. In this study, rats were treated either with three different PFOS doses only (0.6, 1.25 and 2.5mg/kg) or one dose of curcumin (80mg/kg) or three different doses of PFOS combined with 80mg/kg dose of curcumin by gavage for 30days at 48h intervals. We evaluated the DNA damage via comet assay and micronucleus test. Doses of PFOS increased micronucleus frequency (p<0.05) and strongly induced DNA damage in liver in two different parameters; i: the damaged cell percentage and ii: genetic damage index. Curcumin prevented the formation of DNA damage induced by PFOS and curcumin substance applied with PFOS caused a decrease in the micronucleus frequency. PFOS increased apoptotic gene expression but curcumin decreased the expression levels of caspase 3 and 8.