Polymorphisms in Turkish population

Mol Biol Rep. 2011 Mar 9. [Epub ahead of print]

Engin AB, Karahalil B, Engin A, Karakaya AE.

Source

Department of Toxicology, Faculty of Pharmacy, Gazi University, 06330, Hipodrom, Ankara, Turkey, abengin@gmail.com.

Abstract

Although the developmental stages of gastric carcinoma are still not clear, the constantly generated reactive oxygen and nitrogen species (ROS/RNS) may contribute to the process of carcinogenesis by interacting with DNA. 8-oxoguanine DNA glycosylase-1 (OGG1) is an enzyme involved in base excision repair of 8-oxoguanine that is one of the premutagenic lesions generated by ROS in DNA. The bulky adducts, are recognized and repaired by nucleotid excision repair (NER) enzymes, including xeroderma pigmentosum C and D (XPC, XPD). Eligible 106 gastric cancer patients and 116 cancer-free individuals constituted the study and control groups, respectively. Association between OGG1 Ser326Cys, XPC Lys939Gln, XPD Lys751Gln polymorphisms and the susceptibility tho cancer and the oxidative stress status were evaluated. DNA was extracted from peripheral blood cells and genotypes were determined by using PCR-RFLP. Serum nitric oxide, albumin concentrations, total antioxidant status and Helicobacter pylori IgG were determined. Serum albumin and nitric oxide of cancer patients were lower than that of the controls (P < 0.05). None of the evaluated polymorphisms or Helicobacter pylori IgG seropositivity associated with increased risk of gastric cancer, despite of the increased oxidative stress in cancer patients.

Int J Immunogenet. 2011 Jan 4. doi: 10.1111/j.1744-313X.2010.00988.x. [Epub ahead of print]

Coker A, Arman A, Soylu O, Tezel T, Yildirim A.

Source

The Faculty of Science and Letters, Istanbul Kultur University, Istanbul, Turkey The Faculty of Engineering, Marmara University, Istanbul, Turkey The Department of Cardiology, Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey.

Abstract

Inflammation and genetics play a key role in the pathogenesis of atherosclerosis and its clinical result myocardial infarction (MI). Proinflammatory cytokines, IL-1 and IL-6, have been shown to play essential roles in developmental stages of coronary artery plaque formation. The aim of this study was to determine the association between IL-1 [IL-1RN, IL-1β (-511, +3953)], IL-6 [-174, -572, -597] gene polymorphisms and MI in Turkish population. A total of 402 people were participated; 235 healthy control subjects and 167 MI patients (MI < 40, n: 72; MI > 40, n: 95). Polymerase chain reaction (PCR) was used to determine the genotype of IL-1RN, whereas the genotypes of IL-1β (-511, +3953) and IL-6 (-174, -572, -597) were determined using PCR followed with restriction digestion analysis. There was no significant difference between MI and controls for IL-1RN, IL-1β-511, +3953 (P: 0.875, 0.608, 0.442) and IL-6 -174, -572, -597 (P: 0.977, 0.632, 0.584) gene polymorphisms. Lack of association was observed between MI at younger age (MI < 40) and either IL-1RN VNTR, IL-1β-511, +3953 (P: 0.878, 0.732, 0.978) or IL-6 -174, -572, -597 (P: 0.313, 0.654, 0.552) gene polymorphisms. This study demonstrated that there was not any association between IL-1, IL-6 gene variants and MI in Turkish population. In addition, IL-1 and IL-6 gene polymorphisms did not affect MI at younger age (MI < 40) or older age (MI > 40). Thus, IL-1 and IL-6 single nucleotide polymorphisms may not be a risk factor for susceptibility to MI in Turkish population.

Abstract

Distribution and prevalence of germline mutations in BRCA1 and BRCA2 differ among different populations. For the Turkish population, several studies have addressed high-risk breast cancer and ovarian cancer (BC-OC) patients. In most studies, both genes were analyzed in part, and a quite heterogeneous mutation spectrum was observed. For high-risk Turkish prostate cancer (PCa) patients, however, there are no data available about mutations of germline BRCA genes. To accurately determine the contribution of germline mutations in BRCA1 and BRCA2 in Turkish BC, OC, and PCa high-risk patients, 106 high-risk BC-OC patients, 50 high-risk PCa patients, and 50 control subjects were recruited. The study represents the only full screening, to date, of a large series of Turkish high-risk BC-OC patients and the only study in Turkish high-risk PCa patients. Mutation screenings were performed on coding exons of both genes with either denaturing gradient gel electrophoresis or denaturing high performance liquid chromatography, or with both techniques. Three deleterious mutations in BRCA1 and three deleterious mutations in BRCA2 were detected in different BC-OC patients, and one truncating mutation was detected in a high-risk PCa patient. In addition, 28 different unclassified and mostly novel variants were detected in both genes, as well as several silent polymorphisms. These findings reflect the genetic heterogeneity of the Turkish population and are relevant to genetic counseling and clinical management.

Abstract

BACKGROUND: Breast cancer (BC), is more prevalent in subjects who have had prolonged exposure to heterocyclic amines, aromatic amines and high levels of oestradiol. Cytochrome P450 1B1 (CYP1B1) and N-acetyltransferase2 (NAT2) have complementary role in metabolism of xenobiotics such as arylamines and heterocyclic amines, CYP1B1 also hyroxylates 17-beta oestradiol. CYP1B1*3 polymorphism and seven missense and four silent polymorphisms of NAT2 were investigated.

PATIENTS AND METHODS: Sixty Turkish female BC patients and 103 healthy controls were phenotyped by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP). Results and

CONCLUSION: The distribution of NAT2 activity in the healthy control group was found to be correlated with that of healthy caucasians. Patients had slow acetylator phenotypes of NAT2, 1.8 times higher than controls but no statistical differences were found (p=0.07). In addition, the NAT2*5 alelle was more statistically correlated with breast cancer patients rather than the controls (p=0.02). Moreover, NAT2*5B was the most frequent haplotype of the NAT2*5 family (p=0.000). Breast cancer patients were detected to posses more CYP1B1*3 mutant alleles than the controls (p=0.043). The combined effect of CYP1B1*3 polymorphism and NAT2 slow acetylator genotype contributed to an increased risk for breast cancer in patients in this study (p=0.004).