Yazan: admin Tarih: Tem 12th, 2009 | Kategori::
Gene polymorphisms,
polymorphisms
Pharmacogenomics. 2009 May;10(5):769-78.
Gunes A, Ozbey G, Vural EH, Uluoglu C, Scordo MG, Zengil H, Dahl ML.Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden. Arzu.Gunes@medsci.uu.se
AIMS: To study the variation in CYP1A2 activity in relation to smoking, gender, age and CYP1A2 polymorphisms. MATERIALS & METHODS: CYP1A2 activity was determined by plasma paraxanthine:caffeine ratio (17X:137X) 4 h after the intake of a standardized cup of coffee in 146 Turkish healthy volunteers. Seven CYP1A2 polymorphisms (-3860G>A, -3113G>A, -2467del/T, -739T>G, -729C>T, -163C>A and 5347T>C) were analyzed. RESULTS: The 17X:137X ratios were increased in smokers (p < 0.0001) and tended to be higher in men both among nonsmokers (p = 0.051) and smokers (p = 0.064). Age-related differences were observed only among nonsmoking women (p = 0.024). The -163C>A polymorphism correlated with 17X:137X ratios only in smokers (p = 0.006). Furthermore, increased 17X:137X ratios were observed in CYP1A2 haplotype H4 (-3860G, -3113G, -2467del, -739T, -729C, -163A and 5347T) carriers in the overall study population (p = 0.026). Multiple regression analyses including smoking, gender, -163C>A genotype and age revealed a significant influence of smoking (p < 0.0001) and gender (p = 0.002) in the overall study population. However, in nonsmokers only the influence of gender remained significant (p = 0.021), while in smokers the influence of the -163C>A genotype held the statistical significance (p = 0.019). The influence of haplotype H4 remained significant (p = 0.028) in the overall study population in similar analyses. CONCLUSION: Smoking has the strongest impact on CYP1A2 activity, while gender and haplotype H4 showed marginal effects. The influence of the -163C>A polymorphism on CYP1A2 activity in smokers suggests an effect on the inducibility of the enzyme.
Yazan: admin Tarih: Tem 12th, 2009 | Kategori::
Paraoxonase
Folia Biol (Praha). 2009;55(2):35-40
Isbilen E, Yilmaz H, Arzu Ergen H, Unlucerci Y, Isbir T, Gurdol F.
Department of Biochemistry, Faculty of Medicine, Baskent University, Ankara, Turkey.
Paraoxonase 1 (PON1) is thought to influence serum homocysteine concentrations, at least in part, due to its homocysteine thiolactonase activity and to play a role in preeclampsia and atherosclerosis. We investigated the effects of PON 55 and PON 192 polymorphisms on plasma total homocysteine (tHcy) concentrations in preeclamptic and healthy pregnants among Turkish population (N = 106). PON 55 and 192 genotypes were determined by PCR RFLP techniques. Plasma tHcy concentrations were measured by high-performance liquid chromatography. No differences were observed in the distribution of PON 1 55/192 genotypes and allele frequencies between the preeclamptic and healthy pregnants. tHcy level in the plasma of preeclamptic women was found to be increased in comparison with healthy pregnants (P < 0.01). Preeclamptic women bearing the mutated PON 192 RR and wild-type PON1 55 LL genotypes had higher tHcy levels than those of the healthy pregnants with the corresponding genotypes, supporting the possibility that the hyperhomocysteinaemia seen in preeclamptic women is associated with the PON genotypes. However, no influence of the allelic distribution on plasma tHcy concentrations was detected in either group. Our results suggest that PON1 55 and 192 genotypes might have an important role in developing hyperhomocysteinaemia and may also have a role in the pathogenesis of preeclampsia in a Turkish population.
Yazan: admin Tarih: Tem 12th, 2009 | Kategori::
KategorilenmemiÅŸ
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<AA<BB in the PON1 192 polymorphism and LM<LL<MM in the PON1 55 polymorphism. The PON1 192 AA genotype may play an important role as a risk factor for ovarian cancer in the Turkish population and the A and L alleles may be associated with early onset of disease.
