Polymorphisms in Turkish population » Kategorilenmemiş

Combined effect of CYP1B1 codon 432 polymorphism and N-acetyltransferase 2 slow acetylator phenotypes in relation to breast cancer in the Turkish population.

admin — Mon, 29 Nov 2010 23:53:40 +0000

Anticancer Res. 2010 Jul;30(7):2885-9.

Ozbek YK, Oztürk T, Tüzüner BM, Calay Z, Ilvan S, Seyhan FM, Kisakesen HI, Oztürk O, Isbir T.

Department of Molecular Medicine, Institute of Experimental Medicine (DETAE), Istanbul University, Vakif Gureba Cad Sehremini, Istanbul, Turkey.

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).

The APOE -219G/T and +113G/C polymorphisms affect insulin resistance among Turks.

admin — Mon, 29 Nov 2010 23:51:31 +0000

Metabolism. 2010 Aug 17.

N, Laaksonen R, Kähönen M, Hergenc G, Lehtimäki T, Erginel-Unaltuna N.

Department of Genetics, Institute for Experimental Medicine, Istanbul University, 34080, Istanbul, Turkey.

Abstract

The -219G/T (rs405509) and +113G/C (rs440446) polymorphisms within the regulatory region of the apolipoprotein E (APOE) gene have been related to the transcriptional activity of the gene. We examined the effect of the stated polymorphisms and their construct haplotypes with the APOE varepsilon2/varepsilon3/varepsilon4 polymorphism on lipid levels and insulin resistance in the Turkish Adult Risk Factor Study. Randomly selected 1774 adults (mean age, 55.0 +/- 11.7 years; 51.2% women) participating in the population-based Turkish Adult Risk Factor Study were cross-sectionally analyzed for the -219G/T, +113G/C, and varepsilon2/varepsilon3/varepsilon4 polymorphisms as well as their haplotypes. Insulin resistance was defined as the 70th percentile in the sample (>2.51) of the homeostatic model assessment (HOMA). The frequencies of the -219T and +113C alleles were 0.477 and 0.423, respectively; and those of haplotype 1 (GGvarepsilon3) and haplotype 2 (TCvarepsilon3) were 44.1% and 41.9%, respectively. The -219G/T and +113G/C genotypes (both P < .04) and diplotypes of haplotype 2 (TCvarepsilon3) (P < .014) were inversely related to serum fasting insulin and the HOMA index, even after controlling for 8 relevant covariates, but not to serum lipids. Within the APOE3 group, haplotype 2 (TC-/TC+) heterozygotes had an odds ratio of 0.66 (95% confidence interval, 0.42-0.99) for HOMA of insulin resistance after adjusting for 8 covariates. APOE promoter polymorphisms and their diplotypes are independently related with serum fasting insulin levels and HOMA index among Turks.

Association between the T-593A and C6982T polymorphisms of the osteopontin gene and risk of developing nephrolithiasis.

admin — Mon, 29 Nov 2010 23:39:07 +0000

Arch Med Res. 2010 Aug;41(6):442-8.

Gögebakan B, Igci YZ, Arslan A, Igci M, Erturhan S, Oztuzcu S, Sen H, Demiryürek S, Arikoglu H, Cengiz B, Bayraktar R, Yurtseven C, Sarıca K, Demiryürek AT.

Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, Turkey. bgogebakan@gantep.edu.tr

Abstract

BACKGROUND AND AIMS: Increased synthesis of several urinary proteins including osteopontin (OPN) has been shown to be associated with stone formation within the urinary tract. The objective of this study was to analyze the genotype distributions and allele frequencies for OPN gene promoter T-593A and C6982T (in exon 7) polymorphisms among patients with kidney stones.

METHODS: In this case-control study, the study group consisted of 121 patients with radiologically confirmed nephrolithiasis. Genomic DNA from patients and control cases (n = 100) was analyzed by single-strand conformation polymorphism method and nucleotide sequence analysis.

RESULTS: Homozygous carriers of the T-593T genotype were more frequent, but carriers of the A-593A genotype were less frequent in patients than in controls. There was also an increase in -593T allele (88% in patients vs. 79% in controls) and decrease in -593A allele frequencies (21% in control vs. 12% in patients) in the nephrolithiasis groups (p = 0.013). The carriers of C6982C genotype were less frequent, but marked increases in T6982T genotype (25.6% in patients vs. 7% in controls, p = 0.001) and 6982T allele frequency (53.3% in patients vs. 37.5% in controls, p = 0.001) were noted in patients of Turkish ancestry.

CONCLUSIONS: These results are the first to demonstrate the existence of T-593A promoter polymorphism of the OPN gene and significant association with risk of developing nephrolithiasis. Our results showed marked associations between polymorphisms (C6982T and T-593A) of the OPN gene and the stone-forming phenotypes in the Turkish population.

Microsomal epoxide hydrolase polymorphisms

admin — Fri, 23 Jul 2010 14:11:34 +0000

Authors: Hatice Pinarbasi, Yavuz Silig, Ergun Pinarbasi

Affiliations: Department of Biochemistry, Faculty of Medicine, Cumhuriyet University, 58140 Sivas, Turkey. hpinar2658@gmail.com

Doi: 10.3892/mmr_00000324

Pages: 723-727

Abstract:Microsomal epoxide hydrolase plays a dual role in the activation and detoxification of carcinogenic compounds. Two polymorphic sites have been described in exons 3 and 4 of the microsomal epoxide hydrolase gene that change tyrosine residue 113 to histidine (Tyr113His) and histidine 139 to arginine (His139Arg), respectively. The exon 3 polymorphism reduces enzyme activity by approximately 50%, whereas the exon 4 polymorphism causes a 25% increase in activity. In the present study, the distribution of these polymorphisms in a Turkish population including 625 unrelated healthy individuals was examined using a PCR-RFLP method. The observed genotype frequencies of microsomal epoxide hydrolase exon 3 were 54, 38 and 8% for Tyr113Tyr, Tyr113His and His113His, respectively. Exon 4 genotype frequencies were found to be 69, 29 and 2% for His139His, His139Arg and Arg139Arg, respectively.

Association of the G894T Polymorphism of the Endothelial Nitric Oxide Synthase Gene with Diabetic Foot Syndrome Foot Ulcer, Diabetic Complications, and Comorbid Vascular Diseases: A Turkish Case-Control Study.

admin — Fri, 23 Jul 2010 13:59:10 +0000

Genet Test Mol Biomarkers. 2010 Jul 19. [Epub ahead of print]

Corapcioglu D, Sahin M, Emral R, Celebi ZK, Sener O, Gedik VT.

1 Department of Endocrinology and Metabolic Diseases, Faculty of Medicine, Ankara University , Ankara, Turkey .

Abstract

Context: There are controversial results and insufficient knowledge in the literature about the genetics of diabetes mellitus complications in the Turkish population and endothelial nitric oxide synthase (eNOS) gene polymorphisms may act as a potential modifier of diabetic vascular complications. Objective: The objective of this study was to determine the association between eNOS G894T polymorphisms and diabetes-related diseases. Design: A Turkish case-control study was designed. Setting: The study was carried out in the Ankara University Hospital. Patients or Other Participants: Totally, 97 Turkish patients with diabetic foot ulcers and 102 controls were enrolled. Patients who had not received antimicrobial treatment in the preceding 6 months were included. Diabetic patients with hand and/or foot ulcers resulting from major trauma, such as road traffic accidents, were excluded. Main Outcome Measure: The effect of eNOS gene polymorphisms on diabetic complications and comorbid diseases was measured. Results: Regarding eNOS G894T gene polymorphisms, 47.4% of the patients had GG (n = 46), 47.4% (n = 46) had GT, and 5.2% (n = 5) had TT alleles in the diabetes mellitus group, and 47.0% (n = 48), 41.2% (n = 42), and 11.8% (n = 12) had GG, GT, and TT alleles in the control group, respectively. There was no significant difference between the groups regarding the eNOS G894T gene allele ratios. Between groups with and without diabetic complications, a significant difference has only been found in the distribution of alleles in patients with comorbid atherosclerotic heart disease, whose GT-TT alleles were significantly higher than the GG alleles (p = 0.004). Conclusion: G894T polymorphism of eNOS gene was not associated with foot ulcer and diabetic complications, except in the presence of atherosclerotic heart disease.

Vascular endothelial growth factor +405 C/G polymorphism is highly associated with an increased risk of endometriosis in Turkish women.

admin — Fri, 05 Feb 2010 20:43:25 +0000

Arch Gynecol Obstet. 2009 Dec 30.

Altinkaya SO, Ugur M, Ceylaner G, Ozat M, Gungor T, Ceylaner S.

Department of Infertility, Zekai Tahir Burak Women’s Health Care Education and Research Hospital, Ankara, Turkey, altinkayaozlem@yahoo.com.

OBJECTIVE: Endometriosis is a chronic gynecological disease characterized by the growth of hormonally responsive, endometrial tissue outside the uterine cavity. The present study aims to analyze two vascular endothelial growth factor (VEGF) polymorphisms (-460 C/T and +405 C/G) in Turkish women with and without endometriosis. STUDY DESIGN: A case-control study was undertaken at the Infertility Department of Zekai Tahir Burak Women’s Health Care Education and Research Hospital. The single nucleotide polymorphisms, -460 C/T and +405 C/G, in the 5′-untranslated region of the VEGF gene were tested in 98 affected women and 94 women with no laparoscopic evidence of disease. Endometriosis was also confirmed histologically. Following genomic extraction of genomic DNA, genotyping of the -460 C/T and +405 C/G polymorphisms of the VEGF gene were performed by polymerase chain reaction and restriction fragment length polymorphism assay. Nominal data were evaluated by Pearson Chi-square or Fisher’s Exact test, where applicable. Odds ratios and 95% confidence intervals were also calculated. A P value less than 0.05 was considered statistically significant. RESULTS: Demographic data were similar among groups. The genotype and allele frequencies of the -460 C/T polymorphism did not differ significantly between cases and controls. In contrast, the genotype (P < 0.001) and allele frequencies (P < 0.001) of +405 C/G polymorphism showed a significant difference between cases and controls. Regardless of the early or advanced stage, women with endometriosis showed a higher incidence of the +405 GC genotype and +405G allele when compared with the controls. CONCLUSIONS: These data suggest that VEGF +405 GC genotype and +405G allele may be associated with the risk of developing early and advanced stage endometriosis in the Turkish population.

CTLA-4 gene polymorphism of exon 1(+49 A/G) in Turkish systemic lupus erythematosus patients.

admin — Mon, 24 Aug 2009 20:44:32 +0000

Int J Immunogenet. 2009 Aug;36(4):245-50

Ulker M, Yazisiz V, Sallakci N, Avci AB, Sanlioglu S, Yegin O, Terzioglu E.

Akdeniz University Teknocity, Kampus Antalya, Turkey.

Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA-4 +49.

Investigation of PON1 192 and PON1 55 polymorphisms in ovarian cancer patients in Turkish population.

admin — Sun, 12 Jul 2009 06:14:42 +0000

In Vivo. 2009 May-Jun;23(3):421-4.

Arpaci A, Görmüs U, Dalan B, Berkman S, Isbir T.

Department of Molecular Medicine, Istanbul University, Capa, Istanbul, Turkey.

BACKGROUND: Ovarian cancer is the leading cause of death due to gynecological malignancies among women. Oxidative stress is potentially harmful to cells and reactive oxygen species are known to be involved in the initiation and progression of cancer. Paraoxonase (PON1) is an antioxidative enzyme, which eliminates lipid peroxides. PON1 has two common polymorphisms (M/L55 and A/B192) that influence PON1 concentration and activity. PATIENTS AND METHODS: Whether or not the M/L55 or A/B192 genotype relates with ovarian cancer was studied in 51 patients and 54 controls. Polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine these polymorphisms. RESULTS: The proportion of smokers was significantly higher in the patients than the controls (26.9% vs. 7%; Chi-square: 7.81, p:0.005; Odds ratio (OR): 4.88 95% CI: 1.49-15.99). The frequencies of the PON1 192 AA, BB and AB genotypes among the patients were 0.76, 0.12 and 0.12 and among the control subjects, 0.33, 0.11 and 0.56, respectively. The AA genotype frequency was significantly higher in the patients than the controls (Chi-square: 19.242, p=0.000; OR: 2.80 95% CI:1.653-4.757). The frequencies of the PON1 55 LL, MM and LM genotypes among the patients were 0.53, 0.10 and 0.37 and among the control subjects there were 0.46, 0.04 and 0.50, respectively. The MM genotype frequency was higher in the patients than the controls, but not statistically significantly (p>0.05). CONCLUSION: The two polymorphisms were associated with the age of onset of ovarian cancer, which increased in the genotype order AB

Novel GDAP1 Mutation in a Turkish Family with CMT2K (CMT2K with Novel GDAP1 Mutation).

admin — Wed, 29 Apr 2009 19:42:25 +0000

Neuromolecular Med. 2009 Apr 19.

Sahin-Calapoglu N, Tan M, Soyoz M, Calapoglu M, Ozcelik N.

Department of Medical Biology, Faculty of Medicine, Suleyman Demirel University, 32260 Cunur, Isparta, Turkey, nilufersahin@yahoo.com.

Mutations in the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) cause Charcot-Marie-Tooth type 2 (CMT2), a severe autosomal recessive form of neuropathy associated with axonal phenotypes. It has been screened in this study for the presence of mutations in the coding region of GDAP1, which maps to chromosome 8q21, in a family with CMT2. To date, 29 mutations in the GDAP1 have been reported in patients of different ethnic origins. Here, we report a novel missense mutation (c.836A>G), and two polymorphisms: a silent variant (c.102G>C), and a 5′-splice site mutation (IVS5+24C>T) in GDPA1 gene identified in a five generation Turkish family with autosomal recessive CMT2.

Cytotoxic T lymphocyte-associated molecule-4 polymorphism in Turkish patients with Hashimoto thyroiditis.

admin — Wed, 29 Apr 2009 19:33:28 +0000

Int J Immunogenet. 2009 Apr;36(2):103-6.

Sahin M, Gursoy A, Erdogan MF.

Department of Endocrinology and Metabolic Diseases Department, Ankara University School of Medicine, Ibni Sina Hospital, Ankara, Turkey. drsahinmustafa@yahoo.com

We previously shown that in a Turkish population, the A/G polymorphism in exon 1 of the cytotoxic T cell lymphocyte-associated molecule-4 (CTLA-4) gene is associated with Graves’ disease, and that the G allele may contribute to susceptibility for developing Graves’ disease. This polymorphism was identified in 197 patients with Hashimoto thyroiditis (HT) (126 women, 71 men; aged, 42.92 +/- 13.4 years) and 98 healthy individuals (56 women, 21 men; aged, 42.27 +/- 13.43 years) in Turkish population. Polymorphisms were analysed using a polymerase chain reaction-restriction fragment length polymorphism method. Frequency of the A/G genotypes was not significantly different in patients with HT when compared with controls in both sexes (P > 0.05). There was no statistical difference in age, sex, cigarette smoking, initial serum thyroid hormone levels, initial goiter size and thyroid autoantibodies among the patients with the three different genotypes (G/G, A/G and A/A). We concluded that A/G polymorphism of CTLA molecule is linked to occurrence of Graves’ disease bu not to HT in the Turkish population.