The effects of 5-HTTLPR/rs25531 serotonin transporter gene polymorphisms on antisocial personality disorder among criminals in a sample of the Turkish population.

Antisocial personality disorder (ASPD) is a cluster B personality disorder characterized by a disposition for criminal behaviors. It has been determined by previous studies that ASPD may have a genetic origin and the human serotonin transporter gene (SLC6A4) is one of the two serotonergic genes expected to be associated with this disorder. 5-HTT-linked polymorphic promoter region (5-HTTLPR) is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter. Among many polymorphisms in SLC6A4, 5-HTTLPR an insertion/deletion (indel) polymorphism and rs25531 single nucleotide polymorphism (SNP) in the 5-HTTLPR polymorphic region contribute to the regulation of SLC6A4 expression. In this study, we aimed to reveal the relationship between frequencies of 5-HTTLPR variants and ASPD among criminals in the Turkish population. Moreover, it was also attempted to figure out the SLC6A4 gene expression level differences regarding these polymorphisms. The 5-HTTLPR/rs25531 genotypes were determined by PCR and restriction length polymorphism (RFLP) analyses and quantitative real-time-PCR was done for measuring the gene expression levels in the case and control groups. Although no significant difference was observed in the distributions of the 5-HTTLPR/rs25531 polymorphisms between the case and control groups, SLC6A4 expression level in the control group was found significantly higher than the case group (p < 0.0001). There was also no significant difference between genotypes in terms of mRNA expression levels in either the control or the case group. According to our results, ASPD in Turkish society is associated with the SLC6A4 gene expression levels, though the distributions of 5-HTTLPR polymorphisms are not different. This study sheds light on future relevant studies as the first study which is conducted in criminals with ASPD in the Turkish community.

Orexin/hypocretin receptor, Orx1, gene variants are associated with major depressive disorder.

Objective: Orexins (hypocretins) are neuropeptides expressed in hypothalamic neurons and have regulatory roles in feeding/drinking behaviours, endocrine functions and sleep/wakefulness state. Major depressive disorder (MDD) is a major mood disorder and neurotransmitter dysfunction in hypothalamic neurons may have roles in its formation. Hence, we conducted experiments to determine whether orexin receptor 1 and 2 (Orx1, Orx2) genes were associated with MDD development. Methods: Seventy-five MDD patients and 87 healthy controls were enrolled for the study. Genotyping was carried out with real-time polymerase chain reaction (RT-PCR). Hamilton Rating-Scale for Depression (HRSD) and Beck Depression Inventory (BDI) were utilized to evaluate depressive symptom severity. Results: A significant relation was found in genotype frequencies of Orx1 rs10914456 and rs2271933 variants between MDD patients and controls (p = .009, p = .006). Rs10914456 CC genotype increased MDD risk 3.57 times more than carrying other genotypes (p = .008, OR =3.57;95% CI: 1.39-9.14). However, no association was observed in Orx2 rs2653349 genotypes for MDD development (p > .05). Although statistically not significant, HRSD scores were diminished in MDD subjects carrying rs10914456 CC variants when compared with CT and TT variants (p = .069). Conclusion. This study suggests that, Orx1 rs10914456 and rs2271933 can be associated with MDD development. Hence, Orx1 rs10914456 variants may affect depressive symptom severity.

Genetic variants rs1994016 and rs3825807 in ADAMTS7 affect its mRNA expression in atherosclerotic occlusive peripheral arterial disease.

AIM: Peripheral artery disease (PAD) is a vascular disease affecting peripheral circulation. Recently, genome-wide association studies revealed a relationship between single nucleotide polymorphisms (SNPs) in ADAMTS7 (a disintegrin and metalloprotease with thrombospondin motif 7) and atherosclerosis. In this study, we aimed to determine ADAMTS7 expression in peripheral blood mononuclear cells (PBMCs) and the frequency of ADAMTS7 rs1994016 and rs3825807 polymorphisms in a sample of Turkish patients with PAD, and to evaluate the association of matrix metalloproteinase (MMP) levels with PAD development. METHODS: In this case-control study, ADAMTS7mRNA and protein expression was determined using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, respectively, and rs1994016 and rs3825807 variants in ADAMTS7 were determined by real-time PCR in 115 PAD patients and 116 healthy controls. Plasma levels of nine MMPs were determined using a multiplex immunoassay system. RESULTS: ADAMTS7mRNA levels were significantly higher in PAD patients than in controls (t=-2.75, P=.007). There was no significant difference in the frequencies of rs1994016 and rs3825807 between PAD patients and controls (P>.05). In PAD patients, ADAMTS7mRNA levels were significantly increased for the CC genotype of rs1994016 (t=-2.31, P=.026) and TT genotype of rs3825807 (t=-2.23, P=.032). Furthermore, plasma levels of MMP-1, MMP-3, MMP-7, MMP-10, MMP-12, and MMP-13 were significantly higher in PAD patients than in controls (P<.05). CONCLUSION: This is the first report of the relationship between PAD and ADAMTS7 expression and the effects of the rs1994016 and rs3825807 variants on PAD development. ADAMTS7 may be associated with PAD development.

Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.

Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.

Pro198Leu polymorphism in the oxidative stress gene, glutathione peroxidase-1, is associated with a gender-specific risk for panic disorder.

OBJECTIVE: Panic disorder (PD) is an anxiety disorder characterized by sudden attacks of intense fear. Biochemical studies suggest that oxidative stress (OS) index is significantly higher in PD, and OS genes may participate in development of anxiety-like behavioral phenotypes. We aimed to investigate role of polymorphisms in OS gene, glutathione peroxidase-1 (GPX1), and DNA repair enzyme gene, 8-oxoguanine glycosylase-1 (OGG1), in PD patients. METHODS: GPX1 Pro198Leu (rs1050450) and OGG1 Ser326Cys (rs1052133) polymorphisms of 127 patients with PD and 151 disease-free controls were analyzed with real-time polymerase chain reaction. Severity of PD symptoms was assessed by Panic and Agoraphobia Scale (PAS). RESULTS: No significant relationship was found in genotype distributions of OGG1 Ser326Cys and GPX1 Pro198Leu polymorphisms between PD and control groups (p > 0.05). There was no significant relationship between OGG1 or GPX1 polymorphisms, and age of onset, agoraphobia, or PAS scores in PD group (p > 0.05). However, in GPX1 Pro198Leu polymorphism, C allele (Pro) was found to be more frequent in female subgroup of PD patients compared with that in males (p = 0.027). CONCLUSIONS: GPX1 Pro198Leu and OGG1 Ser326Cys polymorphisms were not associated with PD risk in Turkish patients. However, a gender-specific effect of GPX1 Pro198Leu C allele may be associated with PD development.

Association of rs11081062 polymorphism of DLGAP1 gene and levels of SLC1A1 protein with obsessive-compulsive disorder.

Glutamate is an important neurotransmitter known to be effective in obsessive-compulsive disorder (OCD). The aim of this study is to investigate the relationship between the DLGAP1 gene encoding the scaffold protein of ionotropic glutamate receptors and the SLC1A1 gene encoding the glutamate transporter protein with OCD. Study groups consisted of 95 patients with OCD and 100 healthy controls. The severity of OCD in the patient group was determined by using the Y-BOCS. Single nucleotide polymorphisms of rs11081062 (C/T) in DLGAP1 and rs587777696 (C/T) in SLC1A1 were analyzed by real-time PCR. Levels of SLC1A1 protein were determined by ELISA. A significant difference was found between genotype distributions of rs11081062 in DLGAP1 in study groups (p < 0.001). No significant association was found rs587777696 in SLC1A1 in OCD patients and controls. SLC1A1 protein levels were found to be lower in OCD patients compared to controls (p = 0.005). According to OCD risk estimates for genotypes distributions of rs11081062 in DLGAP1, having CT + TT genotypes was associated with the occurrence of sexual and religious obsessions and counting compulsions (p = 0.038, OR = 2.98; p = 0.033, OR = 3.43; p = 0.035, OR = 2.66, respectively). CT genotype in DLGAP1 rs11081062 polymorphism was found to increase the risk of OCD in the female gender (p = 0.042, OR = 3.01). This study suggests that rs11081062 in DLGAP1 may be associated with OCD and that SLC1A1 protein levels may be involved in the occurrence of OCD. We believe that our research can contribute to the understanding of the importance of glutamate in OCD.

Chromosome 9p21 rs10757278 polymorphism is associated with the risk of metabolic syndrome.

Metabolic syndrome (MetS) is a common multifactorial disorder that involves abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. Genome-wide association studies have identified a major risk locus for coronary artery disease and myocardial infarction on chromosome 9p21. Here, we examined the frequency of single nucleotide polymorphisms (SNPs) on chromosome 9p21 in a sample of Turkish patients with MetS and further investigated the correlation between regional SNPs, haplotypes, and MetS. The real-time polymerase chain reaction (RT-PCR) was used to analyze 4 SNPs (rs10757274 A/G, rs2383207 A/G, rs10757278 A/G, rs1333049 C/G) in 291 MetS patients and 247 controls. Analysis of 4 SNPs revealed a significant difference in the genotype distribution for rs2383207, rs10757278, and rs1333049 between MetS patients and controls (p = 0.041, p = 0.005, p = 0.023, respectively) but not for rs10757274 (p = 0.211). MetS and control allelic frequencies for rs2383207, rs10757278, and rs1333049 were statistically different (p < 0.05). The rs2383207 AG variant, was identified as a MetS risk factor (p = 0.012, OR = 33.271; 95 % CI: 2.193-504.805) and the AA haplotype in block 1 and the GC, AG haplotypes in block 2 were associated with MetS (χ(2) = 3.875, p = 0.049; χ(2) = 9.334, p = 0.0022; χ (2) = 9.134, p = 0.0025, respectively). In this study, we found that chromosome 9p21 SNP rs10757278 and related haplotypes correlate with MetS risk. This is the first report showing an association between a 9p21 variant and MetS and suggests that rs10757278 polymorphism may confer increased risk for disease.

Genetic polymorphism of angiotensin I-converting enzyme (ACE), but not angiotensin II type I receptor (ATr1), has a gender-specific role in panic disorder.

AIMS: Angiotensins were shown to have some role in the development of panic disorder (PD). In this study, we aimed to determine the frequency of polymorphisms in two angiotensin-related genes, angiotensin I-converting enzyme (ACE) and angiotensin II type I receptor (ATr1), in a sample of Turkish patients with PD and to evaluate their association with PD development. METHODS: Polymerase chain reaction and restriction fragment length polymorphism was used to analyze ATr1 A1166C polymorphism, and only polymerase chain reaction was used to analyze functional ACE insertion/deletion polymorphism in 123 patients with PD and in 169 similarly aged disease-free controls. RESULTS: There was no significant difference in the genotype distribution between PD patients and controls for each polymorphism (P>0.05). Allele frequency of ACE insertion/deletion was borderline statistically significant between the groups (P=0.055; odds ratio: 1.39; 95% confidence interval: 0.99-1.95), and allele frequency of ATr1 A1166C was not significantly different between the groups (P=0.32; odds ratio: 0.81; 95% confidence interval: 0.53-1.22). CONCLUSION: This study suggests that polymorphisms of ACE I/D and ATr1 A1166C are not associated with risk of PD in Turkish patients. However, in ACE insertion/deletion polymorphism, the insertion allele was found to be more frequent in the male subgroup of patients (χ²=4.61, P=0.032) than in controls, suggesting a potential male-specific role of the less active ACE insertion allele in the pathogenesis of PD.

AGT rs699 and AGTR1 rs5186 gene variants are associated with cardiovascular-related phenotypes in atherosclerotic peripheral arterial obstructive disease.

BACKGROUND: Peripheral arterial diseases (PAD) refer to the arterial diseases other than coronary arteries and the aorta. Atherosclerosis is the major cause of PAD. Renin angiotensin aldosterone system (RAAS)-related genes were associated with cardiovascular diseases. Angiotensin II is the pro-inflammatory, proliferative and vasoconstrictor effector of RAAS in the vascular system. AIMS: In this study, we aimed to investigate whether the effects of the angiotensinogen (AGT) rs699 (M268T), angiotensin-converting enzyme (ACE) I/D (rs1799752), angiotensin II receptor type 1 (AGTR1) (A1166C) rs5186, and angiotensin II receptor type 2 (AGTR2) rs35474657 variants were associated with PAD etiology due to atherosclerotic involvement of aorta-iliac and femoro-popliteal artery occlusions. METHODS: AGT rs699, AGTR1 rs5186, ACE I/D (rs1799752), AGTR2 rs35474657 gene variants were determined by real-time polymerase chain reaction (RT-PCR) in 63 PAD patients (33 femoro-popliteal, 30 aorta-iliac) and 70 healthy controls. RESULTS: Although there was no significant relationship in the genotype frequencies of AGT rs699, AGTR1 rs5186, ACE I/D (rs1799752), and AGTR2 rs35474657 variants between PAD and control groups (p > 0.05), AGT rs699 TT genotype was significantly associated with fasting glucose (p = 0.023) in PAD patients. Besides, CC genotype of rs699 was significantly related with HDL-cholesterol levels (p = 0.020) in PAD group. Furthermore, AGTR1 rs5186 CC genotype carriers demonstrated significantly higher LDL-cholesterol (p = 0.034) and triglycerides levels (p = 0.007). CONCLUSIONS: This report is the first to show an association between RAAS-related gene variants and their relation with the biochemical characteristics of PAD and suggests that RAAS-associated gene variants may have significant roles in cardiovascular related phenotypes of PAD patients.

Catechol-O-Methyltransferase Val158Met and brain-derived neurotrophic factor Val66Met gene polymorphisms in paraphilic sexual offenders.

BACKGROUND: Child sexual abuse (CSA) is an important problem worldwide. The reason of sex abuse is considered as multifactorial. Genetic contribution reported by recent studies is a significant evidence for this pathologic behavior. Catechol-O-Methyltransferase (COMT) is an enzyme in the metabolic inactivation of catecholamine and substances containing catecholamines such as dopamine, epinephrine, and norepinephrine. COMT polymorphism causes functional changes in COMT enzyme activity. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor usually synthesized from central nervous system neurons. With the effect of BDNF, dopamine and serotonin play important roles on neurogenesis, survival, and synaptic plasticity. AIM: This study aims to examine COMT Val158Met (rs4680) and BDNF Val66Met (rs6265) polymorphisms in CSA. SETTINGS AND DESIGN: This was a case-control study. MATERIALS AND METHODS: Seventy paraphilic child sexual abuser patients and seventy age- and gender-matched healthy controls participated in this study. COMT Val158Met and BDNF Val66Met polymorphisms were genotyped by real-time polymerase chain reaction assay. RESULTS: COMT Val158Met genotype frequencies were determined as GG 31.4%, GA 45.7%, and AA 22.9% in patients; GG 24.3%, GA 45.7%, and AA 8.6% in controls; and exhibited a positive relationship between the groups (P = 0.018). BDNF Val66Met genotype frequencies were determined as GG 77.1%, GA 21.4%, and AA 1.4% in patients; GG 65.7%, GA 31.4%, AA 2.9% in controls; and no significant relationship was observed between the groups (P = 0.317). CONCLUSIONS: This research investigated COMT (Val158Met) and BDNF (Val66Met) in paraphilic child sexual offenders. A positive relationship was found for COMT gene; however, no significant relation was observed for BDNF gene between paraphilic sexual offenders and controls.

Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients.

Several inherited polymorphisms are associated with risk of venous thrombosis, including mutation at codon 506 of the factor V gene, mutation at position 20210 of the prothrombin gene, and mutations in the protein C gene. In this study, genotyping for factor V, prothrombin, and protein C mutations was performed in 50 patients and 25 control subjects by polymerase chain reaction-based analysis. The prevalence of factor V and prothrombin mutations was not significantly different from that in the general population. Nine of the patients had heterozygous protein C mutation. There was a high prevalence of the mutated protein C allele in the pulmonary emboli group (42.8%). Protein C mutation incidence was higher in the pulmonary emboli group than in the deep vein thrombosis (8.33%) and cerebral vein thrombosis (16.1%) groups. These results indicate that patients with protein C deficiency have a greater risk of thrombosis than patients with factor V or prothrombin G20210A mutation.

Increased Expression of Interleukin-18 mRNA is Associated with Carotid Artery Stenosis

Background: Carotid artery stenosis is the atherosclerotic narrowing of the proximal internal carotid artery and one of the primary causes of stroke. Elevated expression of the pleiotropic proinflammatory cytokine interleukin-18 has been demonstrated in human atherosclerotic plaques. Aims: To investigate whether the mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 −137 G/C (rs187238) variants are associated with carotid artery stenosis development. Study Design: Case-control study. Methods: The mRNA expression levels of interleukin-18 and interleukin-18-binding protein and interleukin-18 rs187238 variants were evaluated by quantitative real-time polymerase chain reaction and real-time polymerase chain reaction, respectively, in the peripheral blood mononuclear cells of 70 patients with carotid artery stenosis (36 symptomatic, 34 asymptomatic) and 75 healthy controls. Results: Interleukin-18 mRNA expression was significantly increased in carotid artery stenosis patients compared to that in healthy controls (p=0.01). However, no significant difference was observed between interleukin-18-binding protein mRNA expression levels in patients with carotid artery stenosis and those in controls (p=0.101). Internal carotid artery stenosis severity was significantly higher in symptomatic patients than that in asymptomatic patients (p<0.001). A significant relationship was identified between interleukin-18 expression and internal carotid artery stenosis severity in patients with carotid artery stenosis (p=0.051). Interleukin-18 rs187238 polymorphism genotype frequencies did not significantly differ between patients with carotid artery stenosis and controls (p=0.246). A significant difference was identified between interleukin-18-binding protein gene expression and symptomatic and asymptomatic patients (p=0.026), but there was no difference in interleukin-18 expression between the symptomatic and asymptomatic subgroups (p=0.397). Conclusion: Interleukin-18 mRNA expression may affect carotid artery stenosis etiopathogenesis and internal carotid artery stenosis severity and also may play a mechanistic role in the pathogenesis of carotid artery stenosis, influencing the appearance of symptoms.

The investigation of GSTT1, GSTM1 and SOD polymorphism in bladder cancer patients.

Glutathione S transferases (GSTT1, GSTM1, GSTP1) are enzymes that activate the detoxification of endogenous and exogenous agents. The genetic polymorphism in these genes may change the response of individuals to environmental toxicants. The genetic polymorphisms of GSTT1, GSTM1, GSTP1 have been studied extensively in the determination of individual cancer risks. Some studies showed a strong relationship between polymorphism of GSTs and superoxidedismutase enzymes. Using the polymerase chain reaction (PCR) the prevalence of genetic polymorphisms of GSTT1, GSTM1 and MnSOD (Manganese Superoxide Dismurase) was investigated in 104 cases and controls to seek any association with the risk of bladder cancer. The frequency of GSTT1 +/+ polymorphism was 65% (33/51) in the cases and 79% (42/53) in the controls. The frequency of the GSTM1 +/+ polymorphism was 33% (17/51) in the cases and 58% (31/53) in the controls. The frequency of the GSTM1 null genotype was 42% (22/53) in the controls and 68% (34/51) in the patients. The frequency of the SOD AA genotype was 36% (17/51) in the cases and 33% (19/53) in the controls. There was no association between the GSTT1 and SOD polymorphism and bladder cancer incidence. The incidence of the GSTM1 null genotype was increased in bladder cancer patients compared to controls (OR = 1.755, 95% CI = 1.119-2.751).

Upregulation of OLR1 and IL17A genes and their association with blood glucose and lipid levels in femoropopliteal artery disease.

Oxidized low-density lipoprotein receptor 1 (OLR1) and interleukin 17A (IL17A) have pro-inflammatory roles in the development of cardiovascular disorders. The present study evaluated the association of OLR1 and IL17A and their polymorphisms with the development of femoropopliteal (FP) artery disease. The mRNA expression of OLR1 and IL17A in peripheral blood mononuclear cells as well as the frequency of OLR1 rs11053646 and IL17A rs8193037 and rs3819025 polymorphisms were assessed by polymerase chain reaction in 70 patients with FP artery disease and 80 age-matched disease-free controls. Furthermore, the levels of plasma cytokines were assessed by multiplex immunoassay. OLR1 and IL17A mRNA expression was significantly higher in patients with FP artery disease compared with that in controls (P<0.001). No significant difference was observed in the genotypic frequencies of OLR1 rs11053646 (P=0.87) or in IL17A rs8193037 and rs3819025 (P=0.80 and 0.92, respectively) polymorphisms between patients with FP artery disease and controls. Plasma IL4, -6, -10, -22, -31 and -33 as well as soluble cluster of differentiation 40 ligand and tumor necrosis factor-α levels were significantly increased among FP artery disease patients compared with controls (P<0.05). Furthermore, OLR1 expression was positively correlated with triglyceride (r=0.463, P<0.001), low-density lipoprotein cholesterol (r=0.507, P<0.001) and total cholesterol levels (r=0.357, P=0.006) in patients with FP artery disease. To the best of our knowledge, the present study was the first to identify an association between OLR1 and IL17A genes and FP artery disease. OLR1 and IL17A mRNA transcripts may be associated with blood lipid parameters and with the development of FP artery disease.

The role of N-acetylcysteine treatment on anti-oxidative status in patients with type II diabetes mellitus.

The development of diabetic complications has usually been attributed to the nonenzymic glycation of tissue proteins. Only recently, however, have researchers examined the possible role on free radicals in the pathogenesis of diabetes. In the present study, glutathione (GSH) and major antioxidant enzyme levels in plasma of patients with type II diabetes mellitus were assessed both before and after 3 months of N-acetylcysteine (NAC) therapy. Thirty-two diabetic patients were examined as well as fifteen healthy controls. Before treatment with NAC, glutathione peroxidase (GPx), catalase (CAT), and (GSH) levels of diabetic patients and control subjects showed no significant differences, whereas glutathione S-transferase (GST) levels were higher in type II diabetic patients. Following 3 months of Following NAC supplementation, GSH, GST, and CAT levels were found to be similar to the levels before treatment. On the other hand, GPx activity was significantly lower compared with the values before treatment. According to this finding, NAC treatment could have a positive effect on GPx values in type II diabetic patients showing abnormally high values.

Polymorphisms in the long non-coding RNA CDKN2B-AS1 may contribute to higher systolic blood pressure levels in hypertensive patients.

OBJECTIVES: Hypertension (HT) is a complex disorder influenced by both genetic and environmental factors. Recent genome-wide association studies have identified a major risk locus for atherosclerosis on chromosome 9p21.3. SNPs within the coding sequences of CDKN2A/B and the long non-coding RNA CDKN2B-AS1 could potentially contribute to HT development. Thus, this study aimed to investigate whether the frequency of four SNPs on chromosome 9p21.3 affects blood pressure (BP) levels in Turkish HT patients, and to examine correlations between these SNPs, specific SNP haplotypes, and HT. DESIGN AND METHODS: This is a case-control study comparing HT patients and healthy controls. Real-time polymerase chain reaction (RT-PCR) analysis was utilized to detect SNPs rs10757274, rs2383207, rs10757278, and rs1333049 in 170 HT patients and 180 healthy controls. RESULTS: Each SNP was detected at significantly higher frequencies in HT patients than in controls (p values 0.001); however, there was no significant link between rs10757274, rs2383207, rs10757278, and rs1333049 SNPs and HT grades. Furthermore, there was a significant association between elevated systolic BP levels and rs1333049 GG genotype (p=0.047), while weight gain and increased fasting glucose levels were significantly associated with rs2383207 AA genotype (p=0.020 and p=0.009, respectively). Lastly, we detected a correlation between GG, GA, and AG haplotypes in block 1 (rs10757274, rs2383207) and GC and AG haplotypes in block 2 (rs10757278, rs1333049) and HT. CONCLUSIONS: Our findings suggest that SNPs rs10757274, rs2383207, rs10757278, and rs1333049, particularly those within the CDKN2B-AS1 gene, and related haplotypes may confer increased susceptibility to HT development.

Evaluation of effects of melatonin and caffeic acid phenethyl ester on acute potassium dichromate toxicity and genotoxicity in rats.

OBJECTIVE: The aim of this study is to investigate the possible protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on potassium dichromate (K2 Cr2O7)-induced nephrotoxicity and genotoxicity. METHODS: A total of 40 Wistar albino rats were divided into five groups: control, K2Cr2O7(K2Cr2O715 mg/kg, one dose, i.p.), K2Cr2O7 + melatonin, K2Cr2O7 + CAPE, and K2Cr2O7 + melatonin + CAPE. Urine and blood samples were collected from rats before scarification. One kidney was collected for histopathological studies, and the other was stored at -80°C for further determination of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST), and glutathione reductase (GR) levels with spectrophotometric method. Comet assay was used to evaluate the genotoxicity. RESULTS: We observed a significant amelioration in genotoxicity by melatonin and simultaneous melatonin + CAPE treatment compared to K2Cr2O7 group (p1, p2< 0.05). SOD, CAT, GSH, GST, and MDA levels did not change when compared with controls. When K2Cr2O7 applied group was treated with melatonin and CAPE, neither melatonin nor CAPE made any changes in kidney GSH, GST, SOD, and MDA levels (P > 0.05). We noted that treatment with CAPE and melatonin + CAPE together caused a significant decrease in renal tissue damage, an upregulation in the kidney CAT levels (P < 0.05) and a slight healing at GR levels when compared with the K2Cr2O7 group. CONCLUSION: Our results revealed, CAPE and melatonin may have protective effects on K2Cr2O7 induced nephrotoxicity and cellular damage in rats.

Resveratrol can prevent CCl4-induced liver injury by inhibiting Notch signaling pathway.

We investigated whether Notch signaling was increased in an experimental liver fibrosis model and examined the effects of resveratrol on Notch expression. Rats were divided into four groups: the control group, injected with physiological saline; the CCl4 group; the CCl4 plus resveratrol group; and the resveratrol group. After treatment, immunostaining was performed to detect Notch1, Notch3, Notch4, transforming growth factor (TGF)-beta, alpha-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), and proliferating cell nuclear antigen (PCNA), and TUNEL assays were performed to evaluate apoptosis. Sirius red staining was used to detect fibrosis. Samples were also biochemically evaluated for glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation, and protein oxidation. GSH, GPx, and catalase activities were significantly decreased (p⟨0.001) in the CCl4 group. Distinct collagen accumulation was detected around the central vein and portal areas, and numbers of Notch1-, Notch3-, and Notch4-positive cells were significantly increased (p⟨0.001) in fibrotic areas in the CCl4 group. Increased expression of Notch proteins in fibrotic areas may support the role of Notch in mediating signaling associated with liver fibrosis through activation of hepatic stellate and progenitor cells. In contrast, resveratrol prevented liver fibrosis by decreasing lipid peroxidation and may be effective for inhibiting Notch signaling.

The effects of vigabatrin on rat liver antioxidant status.

The anti-epileptic drug vigabatrin was developed as an inhibitor of gamma-aminobutyric acid transaminase, and its ability to increase inhibition in the central nervous system led to its testing in an animal model. In animal models chronic use of vigabatrin is associated with irreversible myelin vacuolation. Antioxidant drugs change the antioxidant capacity of the body. Oxidative stress of the body increased when valproic acid and carbamazepine were used chronically. To assess whether vigabatrin may affect protein oxidation and lipid peroxidation, glutathione, glutathione peroxidase (GPx), and glutathione-S-transferase (GST) levels were studied in the livers of 57 rat fetuses after administration of vigabatrin to the mothers (19 in the first week of pregnancy, 20 in the second week, and 18 in the third week) and in 19 control rat fetuses without vigabatrin. We compared the results of administration of vigabatrin in each group with the controls. Rat fetus protein oxidation in group I (0.686 nmol/mg protein) and group II (0.723 nmol/mg protein) was higher than in the control group (0.388 nmol/mg protein). Lipid peroxidation (0.209, 0.224, 0.253 nmol/mg protein, respectively) and GPx levels (345.4, 329.0, 283.2 nmol/mg protein, respectively) of groups I, II, and III were higher than in the control group (0.104, 167.2 nmol/mg protein, respectively). GST in group II (79.2 nmol/mg protein) and group III (77.8 nmol/mg protein) were not different from that in the control group (78 nmol/mg protein). It was found that vigabatrin affected all the parameters that were studied, especially in group I, which was given the drug in the first week of pregnancy.

Genetic Polymorphism of the Serotonin Transporter Gene, SLC6A4 rs16965628, Is Associated with Obsessive Compulsive Disorder.

Obsessive compulsive disorder (OCD) is a psychiatric disorder characterized by obsessive ideas and compulsive behaviors. Genetic studies have centered on candidate genes involved in OCD etiology related to serotonergic and dopaminergic systems. In this study, the relationship between cathechol-O-methyltransferase (COMT) -287A/G (rs2097063), serotonin transporters 5-HTTLPR I/D, and SLC6A4 rs16965628 polymorphisms in 80 OCD patients and 100 healthy controls was determined. Patients and controls were genotyped for COMT rs2097063 and SLC6A4 rs16965628 polymorphisms by real-time polymerase chain reaction (PCR). The 5-HTTLPR I/D polymorphism was genotyped using PCR and agarose gel electrophoresis. Severity of symptoms was checked with a Yale-Brown Obsession Compulsion Scale (Y-BOCS). When the OCD group and controls were compared, no significant difference was found between COMT -287A/G (rs2097063), 5-HTTLPR I/D polymorphisms, and OCD. However, a significant difference was found between 5-HTT rs16965628 polymorphism and OCD (p=0.025, OR=3.43, 95% CI 1.41-10.35). In addition, the G allele frequency was found to be higher for rs16965628 in the OCD group. No significant difference was observed between COMT -287A/G (rs2097063), SLC6A4 rs16965628, and 5-HTTLPR I/D polymorphisms and Y-BOCS scores (p>0.05). There was also lack of correlation between Yale-Brown scores and gender of OCD patients. On the other hand, combined genotypes of SLC6A4 rs16965628 GG+GC were found to be risk factors for OCD development (p=0.02, OR=3.464; 95% CI 1.214-9.883) in logistic regression analysis adjusted for age and gender. Our findings suggest that subjects carrying the G allele of rs16965628 have genetic susceptibility to OCD. These data are the first to suggest that polymorphism in serotonin transporter (rs16965628) is associated with the development of OCD in the Turkish population.