The Role of Tissue Persistent Organic Pollutants and Genetic Polymorphisms in Patients with Benign and Malignant Kidney Tumors.

This study aimed to explore whether there is an association between environmental exposure to POPs and kidney tumor induction, and whether blood POP concentrations reflect kidney tissue concentrations. POP derivatives were determined in blood, tumor tissue, tumor surrounding tissue, and perirenal fat tissue samples taken from patients who underwent surgery for renal tumors. A voluntary control group was recruited for blood and urine samples as well. Urinary excretions of o,o'-dityrosine, chlorotyrosine, nitrotyrosine, and 8-OHdG were measured in the same patients. The possible role of genetic polymorphisms in CYP1A1, GST isozymes P, M, and T, and hOGG1 genes on the predisposition to renal cancer was investigated. Some POPs have been found to be associated with kidney cancer, as evidenced by their significantly high ORs. 8-OHdG levels were significantly higher compared to the control group. The GSTT1 null polymorphism can be a risk factor for malignant but not for benign kidney tumors.

Blood and tissue levels of persistent organic pollutants and genetic susceptibility in patients with breast cancer.

We investigated possible associations between the internal concentrations of POPs and correlations between blood and tumor tissue concentrations in patients who underwent surgery for breast cancer and breast reduction as controls. Genetic variations in CYP1A1, GSTP1, GSTM1, and GSTT1 and hOGG1 were evaluated to determine whether they represent risk factors for breast cancer. Certain POPs have been found to be associated with breast cancer development. GST-P1 polymorphism represented a significant risk for breast cancer with unadjusted OR. However, the GSTT1 null polymorphism represented a significant risk for breast cancer when OR adjusted for age and smoking status. CYP1A1 polymorphism was a significant risk factor for breast cancer, regardless of whether the OR was adjusted. These results suggest that exposure to certain POPs, GSTT1 and CYP1A1 polymorphisms, age, and smoking status are risk factors for breast cancer. In addition, the blood concentrations of some POPs represent surrogates for breast tissue concentrations.

Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients.

Sexual dysfunction (SD) is a troublesome adverse effect of selective serotonin reuptake inhibitors (SSRIs). A variety of mechanisms might be involved in the occurrence of SD but the exact mechanism is still not clear. Genetic variations among patients treated with SSRIs are strong determinants of intolerance and poor compliance. The present study aimed to determine the relationship between serotonin-2A receptor (HTR2A) gene -1438A/G and 102T/C polymorphisms, serotonin transporter gene (SLC6A4) 5-HTT-linked polymorphic region (5-HTTLPR) insertion/deletion variant and brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphisms and the occurrence of SD adverse effect in major depressive disorder patients treated with citalopram (CIT) or sertraline (SERT). The result from this investigation revealed that the -1438A/G and 102T/C polymorphisms appear to be associated with the SD induced by CIT. It was also demonstrated that patients receiving SERT, carrying T allele of HTR2A or L allele of 5-HTTLPR more likely to experience SD. Most important overall finding of the study is the combined effects of -1438A/G, 102T/C, and 5-HTTLPR polymorphisms. In a logistic regression model, the occurrence of SD increased with the number of risky alleles. As compared with subjects receiving SERT with few risky (≤2) alleles, those with had 5-6 alleles had an increased SD risk. After all, according to these findings, -1438A/G, 102T/C, and 5-HTTLPR polymorphisms could be considered as promising pharmacogenetic biomarkers in CIT/SERT treatment in major depressive disorder (MDD) patients to avoid the occurrence of SD.

A Novel PCR-RFLP Method for Detection of POR*28 Polymorphism and its Genotype/Allele Frequencies in a Turkish Population.

BACKGROUND: The Cytochrome P450 (CYP) enzymes are involved in the metabolism of many endogenous and exogenous substances. They need electrons for their activity. CYP mediated oxidation reactions require cytochrome oxidoreductase (POR) as an electron donor. A common genetic variation identified in the coding region of POR gene (POR*28) leads to an alteration in POR activity by causing amino acid change. The current study aimed to determine the allele and genotype frequencies of POR*28 in a healthy Turkish population by using a novel genotyping assay. METHODS: A novel PCR-RFLP assay was developed for the detection of POR*28 (rs1057868) polymorphism and the obtained frequencies were compared with the data established in various ethnic groups. RESULTS: Genotypic analysis revealed that of 209 healthy, unrelated individuals tested for POR*28 polymorphism, 55.5% of the studied subjects were homozygous for the CC genotype, 34.9% were heterozygous for the CT genotype and 9.6% were homozygous for the TT genotype. The allele frequencies were 0.73 (C) and 0.27 (T). The present results were in accordance with the Hardy- Weinberg equilibrium. The distribution of POR*28 allele varies between populations. The frequency of the T allele among members of the Turkish population was similar to frequencies in Caucasian populations but was lower than in Japanese and Chinese populations. CONCLUSIONS: In this study, a novel method was developed, which could be applied easily in every laboratory for the genotyping of POR *28 polymorphism. The developed genotyping method and documented allele frequencies may have potential in understanding and predicting the variations in drug response/adverse reactions in pharmacotherapy and susceptibility to diseases in POR-mediated metabolism reactions.