Potential Protective Role of SDF-1 and CXCR4 Gene Variants in the Development of Dementia.

BACKGROUND: The aim of this study was to evaluate the role of polymorphisms of stromal cell-derived factor-1 (SDF-1) and chemokine receptor-4 (CXCR4) genes in dementia susceptibility in a Turkish population. SUBJECTS AND METHODS: The study group included 61 dementia patients, while the control group comprised 82 healthy individuals. Gene polymorphisms of SDF-1 3'A G801A (rs1801157) and CXCR4 C138T (rs2228014) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: A significantly reduced risk for developing dementia was found for the group bearing an A allele for SDF-1 3'A polymorphism (p=0.009; χ2=6.812; OR=0.626; 95%CI= 0.429-0.913). The frequency of the CXCR4 TT and TC genotype was significantly lower in patients with dementia compared to controls (p=0.028; χ2=5.583; OR=0.215; 95%CI=0.05-0.914); (p=0.027; χ2=4.919; OR=0.484; 95% CI=0.246-0.955). Additionally, combined genotype analysis showed that the frequency of SDF1 GA-CXCR4 CC was significantly lower in patients with dementia in comparison with those of controls (p=0.049; OR=0.560; 95% CI= 0.307±1.020). CONCLUSIONS: Our study provides new evidence that SDF1 A and CXCR4 T alleles may be associated with a decreased dementia risk. The present study is important because to our knowledge, it is the first one to be conducted in a Turkish population to date, but we believe that more patients and controls are needed to obtain statistically significant results.

Paraoxonase1 192 (PON1 192) gene polymorphism and serum paraoxonase activity in panic disorder patients.

BACKGROUND/AIM: Reactive oxygen species (ROS) are involved in the development of certain neuropsychiatric disorders. Paraoxonase 1 (PON1) activity has been suggested to be adversely related to oxidative stress in plasma. The purpose of the present study was to demonstrate the relationship between serum PON1 activity and PON1 192 polymorphism in panic disorder (PD). MATERIALS AND METHODS: Fourty-two patients with PD and 46 healthy controls were included in this study. PON1 192 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. PON1 activity was measured by spectrophotometric assay of p-nitrophenol production following the addition of paraoxon. RESULTS: PON1 192 AA genotype and A allele in PD were significantly higher than in the control group, whereas the B allele was found to be significantly higher in the control group. Patients with panic disorder have lower PON1 activity than the control group. CONCLUSION: The PON1 192 AA genotype may increase the risk of PD depending on lipid peroxidation.

Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking.

BACKGROUND: Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Based on this hypothesis, the relationship between APE1 polymorphism, smoking and the risk of lung cancer was explored. MATERIALS AND METHODS: The distribution of the APE1 Asp148Glu polymorphisms in 98 lung cancer patients and 67 healthy individuals were compared using PCR-RFLP analysis. RESULTS: Individuals carrying the APE1 Asp148Glu heterozygous and homozygous variant genotype had a 3.23-fold increased risk of lung cancer compared with these carrying the wild-type (Asp/Asp) genotype (p<0.0001), and those carrying the 148Glu homozygous genotype had a 3.17-fold increased risk (p=0.023). When stratified by smoking status, carriers of the Glu allele of APE1 were at a statistically increased risk of lung cancer among smokers (p=0.001). CONCLUSION: A statistically significant interaction of current smoking status with APE1 Asp148Glu polymorphism was found. These results suggest that the presence of one or two APE1 Glu allele was associated with the risk of developing lung cancer.

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

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

The relationship of oral disturbances of diabetes mellitus patients with paraoxonase gene polymorphisms.

Diabetes Mellitus (DM) is a multisystemic disorder with serious complications and these patients may also have serious problems with their oral cavity probably because of the microangiopathic and neuropathic complications. In diabetic patients, there may be several problems of the oral cavity such as gingivitis, periodontitis, candidiasis, glossitis, oral ulcerations, loss of taste sensations, opportunistic infections and several other conditions dependent on these. One of the recent theories about complications in DM is the contribution of reactive oxygen radicals. Paraoxonase (PON1) is an enzyme that is synthesized in liver and having the capability of hydrolasing the active metabolite of an insectisid, parathion. Previously it was shown that there are two polymorphic areas on the PON1 gene: one causing a Leu --> Met substitution at 55th position, the other causing Gln --> Arg at the 192nd position. We investigated the differences in PON activities related to the oral lesions in Type 2 diabetics and control subjects to see their relationships with PON1 activity levels and the two main gene polymorphisms of PON1 genes, PON1 192 and PON1 55. We had 51 patients and 53 healthy subjects used in the study. PON activity was significantly decreased in Type 2 DM group compared to the control group. Neither PON1 192 nor PON1 55 genotypes had any differential effect on PON1 enzyme activity levels in either group. However, we found that PON1 55 M allele carriers had greater risk for general periodontal and/or gingival problems.

Fas-1377A/G and FasL-844 T/C gene polymorphisms and epithelial ovarian cancer.

BACKGROUND: The Fas receptor is known to be widely expressed in various tissues and FasL is highly expressed on cells of the immune system and also on cells of immune-privileged areas such as the eyes and brain. Ovarian cells are known to exhibit marked FasL immunoreactivity throughout follicular development; there may also be a relationship between Fas and FasL polymorphisms and the immune privileges of the epithelial ovarian cells. PATIENTS AND METHODS: The study included 47 epithelial ovarian carcinoma patients and 41 healthy subjects. Polymerase chain reaction (PCR) and restriction endonucleases were used to determine the polymorphic Fas and FasL genes. RESULTS: The FasL CC genotype was found to increase the risk of ovarian carcinoma and a protective effect of the GGCT genotype was observed. CONCLUSION: Because of the expressional aspects of the FasL-844T --> C polymorphism, individuals carrying the FasL-844C allele would be expected to have higher FasL expression on tumour cells compared with those carrying the FasL-844T allele. People with such a genotype show a tendency to develop various tumours.