Muradiye Nacak

Human arylamine N-acetyltransferase 2 polymorphism and susceptibility to allergic contact dermatitis.

Background  N‐acetyltransferase 2 (NAT2) polymorphism may be involved in the pathogenesis of allergic contact dermatitis.

Association of insertion/deletion polymorphism of the angiotensin‐converting enzyme gene with psoriasis

Background  Genetic factors are likely to be of fundamental importance in the pathogenesis of psoriasis. There are reports concerning the induction or/and exacerbation of psoriasis by angiotensin‐converting enzyme (ACE) inhibitors, which have been attributed to the ACE inhibitor‐induced augmentation of kinin levels in skin. However, to the best of our knowledge there has been no molecular genetic study investigating whether ACE insertion/deletion (I/D) polymorphism may contribute to the genetic background in psoriasis.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey.

Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. We investigated an insertion/deletion (I/D) polymorphism of the gene for ACE in relation to cardiovascular, cerebrovascular, neurodegenerative, and inflammatory diseases. The purpose of the present study was to investigate a possible association between lung cancer and insertion/deletion polymorphism of the ACE gene. A total of 125 patients with lung cancer and 165 control subjects were enrolled in the present study. ACE I/D genotypes were determined by polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control subjects (ACE II genotype 29.6 vs. 17.6%, P = 0.011; ACE I allele 49.6 vs. 39.4%, P =0.009). Our data suggest that the ACE I/D polymorphism could be a risk factor for patients with lung cancer.

Analysis of Dopamine D2 Receptor (DRD2) Gene Polymorphisms in Cannabinoid Addicts

Abstract:  The gene encoding the dopamine D2 receptor (DRD2) has been suggested as a candidate gene for substance dependence. In this study, the possible association between Taq1A and Taq1B DRD2 polymorphisms and cannabinoid dependence was investigated. One hundred and twelve cannabinoid addicted and 130 healthy control subjects were included in this study. The Taq1A and Taq1B genotypes were determined in all subjects by polymerase chain reaction. For each polymorphism (A or B), the subjects were categorized into three groups according to their genotype, that is, the subjects with alleles A1/A1, A1/A2, A2/A2; B1/B1, B1/B2, and B2/B2. A significant association was found between Taq1A gene polymorphism and cannabinoid addicts compared to the control subjects. This finding suggests that polymorphism of the Taq1A, but not the Taq1B, may be associated with the susceptibility to cannabinoid dependence. Further clinical studies are required to be carried out for confirmation and evaluation of these findings.

Childhood Obesity and the Role of Dopamine D2 Receptor and Cannabinoid Receptor-1 Gene Polymorphisms

AIMS The dopaminergic and endocannabinoid systems are involved in regulation of feeding behavior. The aim of the study is to examine the possible relation between polymorphisms of the dopamine D2 receptor (DRD2) and cannabinoid receptor-1 (CNR1) genes and childhood obesity. METHODS A hundred obese children and 100 healthy controls were analyzed for DRD2 Taq1A and Taq1B and CNR1 1359G/A polymorphisms. Genotyping was performed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS There were no statistically significant differences in DRD2 Taq1A and DRD2 Taq1B genotypes or allelic frequencies between obese children and controls (p>0.05). In patients with Taq1B2 allele, morbid obesity was less frequent (p=0.010). The frequency of the A allele of CNR1 1359G/A polymorphism was significantly higher in obese children than in controls (21.0% vs. 13.0%, p=0.0166). The frequency of genotypes AG and GG of the CNR1 1359G/A SNP was different between obese children and control subjects (for AG: 34.0% vs. 22.0%, p=0.0294; for GG: 62.0% vs. 76.0%, p=0.0162, respectively). CONCLUSIONS No significant difference was found between genotypes and alleles of DRD2 Taq1A and DRD2 Taq1B polymorphism in patients and controls, while the CNR1 receptor 1359G/A polymorphism and the presence of the A allele may be one risk factor for susceptibility to obesity.

Mitochondrial uncoupling protein 2 (UCP2) gene polymorphisms are associated with childhood obesity and related metabolic disorders

Abstract Objective: This study aimed to investigate the possible role of uncoupling protein 2 (UCP2) gene polymorphisms in childhood obesity and related metabolic disorders. Methods: Obese patients (n=100) and healthy controls (n=100) were analyzed for -866G>A and insertion/deletion (I/D) polymorphisms of the UCP2 gene by polymerase chain raction and/or restriction fragment length polymorphism. Results: UCP2 I/D polymorphism showed an association with obesity. The insertion homozygous genotype (II) was higher in obese patients (p=0.0001), while the DD genotype was higher in controls (p=0.0034). Body mass index and relative weight were lower in patients carrying the A allele of the -866G>A polymorphism (p=0.021 and p=0.047, respectively). There was an association between insulin resistance and –866A allele carrier patients with consanguineous parents (p=0.005). Conclusion: Insertion homozygous genotype and the allele of I/D polymorphism were found to be risk factors for childhood obesity and related metabolic disorders. The -866A allele was associated with susceptibility to central adiposity, hypercholesterolemia, hypertriglyceridemia and insulin resistance.

Angiotensin-Converting Enzyme Insertion-Deletion Polymorphism in Primary Open-Angle Glaucoma

Purpose: To investigate the hypothesis that primary open-angle glaucoma (POAG) is associated with a common insertion-deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene. Methods: ACE I/D polymorphism was investigated in a control group of healthy subjects (n = 101) and in a group of patients diagnosed with POAG (n = 104). Polymerase chain reaction detection of I/D polymorphism was used to determine the presence of the two ACE alleles in the groups. Results: Neither the I/D genotype distributions nor the allele frequencies differed significantly between POAG and control subjects (DD genotype 34.6 vs. 39.6%; ID genotype 53.9 vs. 40.6%; II genotype 11.5 vs. 19.8%, p = 0.1; D allele 61.5 vs. 60%; I allele 38.5 vs. 40%, p = 0.8). Conclusion: We could not identify a possible association of the I/D polymorphism in the ACE gene with POAG, however further studies with larger patient numbers in different populations are required to clarify the role of ACE gene in susceptibility to POAG.

An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population

Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual.

Effects of caffeine on placental total nitrite concentration: A 21-day, vehicle-controlled study in rats.

BACKGROUND Nitric oxide (NO) is a potent vasodilator that might have an10 important role in the modulation of maternal and fetal vascular tone during pregnancy. The effects of caffeine intake on maternal and fetal hemodynamic properties during pregnancy have been investigated in several human and animal studies. However, based on a literature search, there has been no study of placental total nitrite (a stable product of NO) concentration (PTNC) in pregnant humans or rats given caffeine. OBJECTIVE The aim of this study was to assess the effects of caffeine intake 10 on PTNC in rats. METHODS This 21-day, vehicle-controlled study was conducted at the Department10 of Pharmacology, Gaziantep University Hospital, Gaziantep, Turkey. Female Wistar rats were randomly assigned; based on age and weight, to receive 25, 50, or 100 mg/kg QD caffeine or 50 mg/kg QD isotonic saline solution (vehicle; age-matched control group), intraperitoneally for 21 days. After euthanization of the rats and cesarean section, the numbers of fetuses and fetal deaths were counted. The lengths and weights of the fetuses in each study group were noted. PTNC in the rats was determined using the Greiss reaction. RESULTS This study included 26 rats (7, 7, and 6 rats in the groups receiving10 25, 50, and 100 mg/kg. d caffeine, respectively; 6 rats in the control group). The mean (SD) lengths of the fetuses of the rats given 25, 50, and 100 mg/kg · d caffeine (4.90 [0.15], 4.02 [0.27], and 3.45 [0.17] mm, respectively) were significantly less compared with controls (5.10 [0.18] mm) (all, P < 0.001), as were the mean (SD) weights of the fetuses of rats given caffeine (5.86 [0.24], 4.97 [0.59], and 3.41 [0.23] g, respectively) versus controls (6.18 [0.21] g) (all, P < 0.001). The mean (SD) PTNCs in rats given 25, 50, and 100 mg/kg. d caffeine (19.82 [1.97], 29.39 [2.07], and 45.51 [7.66] nmol/g, respectively) were significantly higher compared with controls (16.10 [2.12] nmol/g) (all, P < 0.001). CONCLUSIONS The results of this study in rats suggest that caffeine intake 10 might increase NO production in the placenta. In addition, based on our findings and those from previous studies, we suggest that this increase might be an adaptive physiologic response to prevent undesirable effects of caffeine on vascular tone during pregnancy.

Relationship between the 1359 G/A polymorphism of the Central Cannabinoid Receptor 1 (CNR1) gene and susceptibility to cannabis addiction in a Turkish population

In this study, we investigate the existence of a possible genetic association between 1359 G/A polymorphism of the Central Cannabinoid Receptor 1 (CNR1) Gene CNR1 (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) and cannabis addiction. DNA samples used in this work are purified from venous leukocytes of 145 unrelated Turkish cannabis-dependent subjects and 140 Turkish control subjects. No significant difference is observed in genotype or allele frequencies of CNR1 1359 G/A polymorphism between these two groups. We also compared CNR1 1359 G/A polymorphism allele frequency distribution in our healthy Turkish population with other healthy populations. The comparison of healthy Turkish subjects with the healthy subjects from English-Irish, Chinese, European-American, African-American, Italian, German and Japanese populations revealed significant differences in allele frequencies. Data indicate that the 1359 G/A CNR1 polymorphism does not contribute to susceptibility to cannabinoid addiction in Turkish subjects. To the best of our knowledge, this is the first study on 1359 G/A CNR1 polymorphism in the Turkish population.