Polymorphisms in Turkish population

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

Turkiye Klinikleri J Med Sci 2004, 24:573-578

Dr. Nurten ERDAL,^a Dr. M. Emin ERDAL,^b Dr. Kaan SAVAŞOĞLU,^b Tuba GÖKDOĞAN^b
aBiyofizik AD, ^bTıbbi Biyoloji ve Genetik AD, Mersin Üniversitesi Tıp Fakültesi, MERSİN

Objective: X-ray repair cross-complementing (XRCC1) is one of the genes responsible for the DNA repair mechanism. It plays an important role in the protection of the integrity of the genome and in the development of mutations in hereditary genetic disease and cancer. The XRCC1 gene codes proteins which play a role in the repair of DNA strand breaks caused by active oxygen, ionization and alkylating agents. Functional polymorphism of the XRCC1 gene is a contributing factor for changes in the DNA repair mechanism, which is a risk factor for cancer.
Material and Methods: Codon 194 (Arg→Trp) and codon 399 (Arg→Gln) are functional polymorphisms in the XRCC1 gene. These polymorphisms were determined by Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in unrelated 75 healty persons. These results were compared with other related investigation results.
Results: Frequencies of Arg and Trp alleles of codon 194 were shown to be 0.94 and 0.06, respectively. However, frequencies of Arg and Gln alleles of codon 399 were 0.65 and 0.35.
Conclusion: With regard to Arg194Trp functional polymorphisms of the XRCC1 gene, our results of allele frequencies are similar to those found in related investigations in American (caucasian) and Colombian populations, but different from others in Taiwanese, American (African-American) and Chinese populations. The other XRCC1 gene polymorphism examined, Arg399Gln, manifested frequencies similar to those found in investigations in Italian, American (caucasian), Finnish and Colombian populations; however, our results are different from those involving Taiwanese, American (African-American), Colombian, Asian and Chinese populations. The alleles at risk appear to vary in different populations and according to cancer type. Therefore, it is very important to determine those alleles exhibiting a heightened cancer risk in our population.

Keywords: Genes, polymorphism, XRCC1 protein

Turkiye Klinikleri J Med Sci 2004, 24:573-578