Analysis of transforming growth factor beta 1 (TGF-beta1) gene polymorphisms in Turkish patients with scleroderma.

Yazan: admin Tarih: Tem 23rd, 2010 | Kategori:: Gene polymorphisms

Cell Biochem Funct. 2010 Jun;28(4):274-7.

Büyük U, Ates O, Dalyan L, Müsellim B, Ongen G, Topal-Sarikaya A.

Department of Molecular Biology and Genetics, Istanbul University, Turkey. atopal@istanbul.edu.tr

Abstract

Systemic sclerosis (SSc) is an autoimmune disease characterized by inflammation and fibrosis of the skin and visceral organs. Fibrosis associated with SSc is characterized by an increased synthesis of a wide range of extracellular matrix (ECM). TGF-beta is a pluripotent cytokine in a wide range of cell types. In particular it has been found to be a potent inducer of ECM protein synthesis and fibroblast migration. The TGF-beta1 gene is highly polymorphic and two signal sequence polymorphisms at codon 10 and codon 25 are linked to disease outcomes. In this study, we analysed two polymorphic sites of the TGF-beta1 gene, codon 10 and codon 25, in 43 Turkish SSc female patients with interstitial lung involvement and in 75 healty individuals by ARMS-PCR. In our study no significant difference was found in codon 10, codon 25 genotype frequencies between patient with SSc and the control group (p = 0.676, 0.375, respectively). Our findings suggest that codon 10 and 25 polymorphism cannot be related with SSc for Turkish population. 2010 John Wiley & Sons, Ltd.


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Analysis of paraoxonase 1 (PON1) genetic polymorphisms and activities as risk factors for ischemic stroke in Turkish population

Yazan: admin Tarih: Oca 21st, 2010 | Kategori:: Paraoxonase

Author(s): Demirdogen BC (Demirdogen, Birsen Can)1, Demirkaya S (Demirkaya, Seref)2, Turkanoglu A (Turkanoglu, Aysun)1, Bek S (Bek, Semai)2, Arinc E (Arinc, Emel)1, Adali O (Adali, Orhan)1
Source: CELL BIOCHEMISTRY AND FUNCTION Volume: 27 Issue: 8 Pages: 558-567 Published: DEC 2009

Abstract: Background Paraoxonase 1 (PON1) is protective against the development of atherosclerosis. a risk factor for ischemic stroke. PON1 gene has one promoter region (-107T/C) and two coding region (192Q/R and 55L/M) polymorphisms that affect the levels and catalytic efficiency of the enzyme. respectively. In this study. we aimed to determine the importance of -107T/C. 192Q/R and 55L/M polymorphisms of PON1 gene and three PON1 activity (diazoxonase, paraoxonase, arylesterase) as risk factors for ischemic stroke
Methods Stud population was comprised of 172 unrelated adult Caucasian patients with acute hemispheric ischemic stroke and 105 symptom-free controls. Genotypes were attained by PCR followed by restriction enzyme digestion and phenotypes were determined by spectrophotometric assays.

Results This is the first study analyzing diazoxonase activity as a risk factor for ischemic stroke Nevertheless, diazoxonase, paraoxonase and arylesterase activities were almost the manic in stroke patients and controls The 107TT genotype was associated with a 1 97 times increased risk for stroke in elderly (age > 59). Individuals with this genotype were found to have the lowest PON1 enzyme activities among the -107T/C genotypes Triple combined haplotype QRLMTC was found to be 6.94- and 10.4-times protective against ischemic stroke in the overall and the elderly Population. respectively. 55LL genotype was associated with 1 78-fold increase in the risk of ischemic stroke

Conclusion PON1 genotypes, but not activities, are related with the risk of stroke. Copyright (C) 2009 John Wiley & Sons, Ltd

Document Type: Article
Language: English
Author Keywords: genotype; paraoxonase; PON1; polymorphism; stroke
KeyWords Plus: HUMAN-SERUM PARAOXONASE; LOW-DENSITY-LIPOPROTEIN; INTIMA-MEDIA THICKNESS; LIPID-PEROXIDATION; LDL OXIDATION; ARYLESTERASE; PROMOTER; PROTEIN; ATHEROSCLEROSIS; CHOLESTEROL
Reprint Address: Demirdogen, BC (reprint author), Refik Saydam Natl Publ Hlth Agcy, Directorate Food Safety & Nutr Res, Ankara, Turkey
Addresses:
1. Middle E Tech Univ, Dept Biochem, Inst Nat & Appl Sci, TR-06531 Ankara, Turkey
2. Gulhane Mil Med Acad, Dept Neurol, Ankara, Turkey


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Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population.

Yazan: admin Tarih: Ağu 14th, 2008 | Kategori:: CYP2C19, CYP2D6

Clin Pharmacol Ther. 1999 Aug;66(2):185-92.

Aynacioglu AS, Sachse C, Bozkurt A, Kortunay S, Nacak M, Schröder T, Kayaalp SO, Roots I, Brockmöller J.

Institute of Clinical Pharmacology, University Clinic Charité, Humboldt University, Berlin, Germany.

BACKGROUND AND OBJECTIVES: The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to the metabolism of about 30% of all drugs. For analysis of the ethnic-related differences in drug disposition and as a preparation for routine genotyping, we examined CYP2C19 and CYP2D6 mutations in a large Turkish population. Methods: CYP2C19 and CYP2D6 alleles were determined with use of genomic deoxyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays. RESULTS: From 404 subjects genotyped for CYP2C19, allele frequencies of CYP2C19*1 (wt), CYP2C19*2 (ml), and CYP2C19*3 (m2) were 0.88, 0.12, and 0.004, respectively; mutations m3 and m4 were not found. Four individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly lower frequency compared to Middle European populations. Among 404 subjects genotyped for CYP2D6, most frequent alleles were CYP2D6*1 (allele frequency 0.37), *2 (0.35), *4 (0.11), *10 (0.06), duplications *1×2, *2×2, or *4×2 (0.06), *5 (0.01), and *17(0.01). Overall, six subjects (1.49%) were predicted to be CYP2D6 poor metabolizers, and 35 subjects (8.66%) were predicted to be ultrarapid metabolizers as a result of CYP2D6 gene duplications. CONCLUSION: Obviously, within Europe there is a north-south gradient, with decreasing frequency of poor metabolizers of CYP2C19 and CYP2D6 to the south and a corresponding increase of ultrarapid metabolizers of CYP2D6. As in other white groups, only CYP2C19*2 plays a relevant role for the CYP2C19 poor metabolizer phenotype. The mutational spectrum of CYP2D6 indicated partial ethnic relationships to Asian and African populations.


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