Nurten Erdal

Significance of catechol-O-methyltransferase gene polymorphism in fibromyalgia syndrome

Abstract. Fibromyalgia syndrome (FS) is associated with a neuroendocrinal disorder characterized by abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis, including hyperactive adrenocorticotropic hormone (ACTH) release and adrenal hyporesponsiveness. Catechol-O-methyltransferase (COMT) enzyme inactivates catecholamines and catecholamine-containing drugs. Polymorphism in the gene encodes for the COMT enzyme. For this study, the significance of COMT polymorphism was assessed in FS. There were three polymorphisms of the COMT gene: LL, LH, and HH. The analysis of COMT polymorphism was performed using polymerase chain reaction (PCR). Sixty-one patients with FS and 61 healthy volunteers were included in the study. Although no significant difference was found between LL and LH separately, the LL and LH genotypes together were more highly represented in patients than controls (P=0.024). In addition, HH genotypes in patients were significantly lower than in the control groups (P=0.04). There was no significant difference between COMT polymorphism and psychiatric status of the patients as assessed by several psychiatric tests (P>0.05). In conclusion, COMT polymorphism is of potential pharmacological importance regarding individual differences in the metabolism of catechol drugs and may also be involved in the pathogenesis and treatment of FS through adrenergic mechanisms as well as genetic predisposition to FS.

Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder

The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.

No Evidence for an Association between the T102C and 1438 G/A Polymorphisms of the Serotonin 2A Receptor Gene in Attention Deficit/Hyperactivity Disorder in a Turkish Population

Disturbances in the serotonergic neurotransmission system have been implicated in the etiology of attenion deficit/hyperactivity disorder (ADHD). As the importance of genetic factors is well established, genes encoding for proteins of the serotonergic pathway are important candidates to unravel the underlying genetic contribution. We previously demonstrated that the polymorphisms of the serotonin transporter gene promoter and regions of variable number of tandem repeats were involved in the pathogenesis of ADHD. The purpose of this study was to examine the relationship between ADHD and two polymorphisms (T102C and 1438 G/A) in the 5-HT2A gene in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 70 patients with ADHD and in 100 healthy controls. There was no significant difference between the frequencies of the T, C, G and A alleles of both groups. No association was found between the studied polymorphisms of the 5-HT2A gene and ADHD in this sample consisting of Turkish children. Overall, our results suggest that the investigated 5-HT2A polymorphisms are not major susceptibility factors in the etiology of ADHD.

Effects of 2.4 GHz radiofrequency radiation emitted from Wi-Fi equipment on microRNA expression in brain tissue

Abstract Purpose: MicroRNAs (miRNA) play a paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. However, their interaction with radiofrequencies is still unknown. The aim of this study was to investigate the long-term effects of radiofrequency radiation emitted from a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue. Materials and methods: The study was carried out on 16 Wistar Albino adult male rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8). Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation for 24 hours a day for 12 months (one year). The same procedure was applied to the rats in the sham group except the Wi-Fi system was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in detail. Results: The results revealed that long-term exposure of 2.4 GHz Wi-Fi radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p* = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3 times and miR- 106b-5p expression is 3.65 times lower in the exposure group than in the control group. However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in brain were not altered. Conclusion: Long-term exposure of 2.4 GHz RF may lead to adverse effects such as neurodegenerative diseases originated from the alteration of some miRNA expression and more studies should be devoted to the effects of RF radiation on miRNA expression levels.

The effect of insulin therapy on biomechanical deterioration of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus in rats

AIMS To investigate the effect of insulin therapy on biomechanical properties of bone in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) in rats. METHODS A total of 28 male Wistar-Albino rats (12-week-old; 210-300g) were divided into 4 groups (n=7 for each) including control [C; no treatment], sham [Sh; distilled water i.p., for 8 weeks], diabetes [T1DM; 65mg/kg of STZ, single i.p.] and diabetes+insulin treatment [T1DM+I; 65mg/kg of STZ, single i.p.+insulin; 2-4UI/day/rat, i.p., for 8 weeks] groups. Body weight, blood glucose levels (BGLs), bone mineral density (BMD) and geometric/mechanical properties of bone tissue were evaluated. RESULTS BGLs in diabetic rats were significantly increased compared to non-diabetic rats, while the body weights were decreased (p<0.05). Femur length and cross-sectional area of femur were significantly decreased in both T1DM and T1DM+I groups (p<0.05). The significant reduction obtained in BMD in T1DM rats compared with C and Sh (p<0.05) groups was reversed by insulin treatment (p<0.05). Displacement, absorbed energy, maximum load, ultimate stress and toughness were significantly decreased inT1DM and T1DM+I groups compared to C and Sh groups (p<0.05). CONCLUSIONS In conclusion, insulin treatment seems to be ineffective in restoration of biomechanical deterioration of bone specific to STZ-induced T1DM.

T102C Polymorphisms at the 5-HT2A Receptor Gene in Turkish Schizophrenia Patients: A Possible Association with Prognosis

Background: Serotonergic system abnormalities have been implicated in the pathogenesis of schizophrenia. The 5-HT2A receptor gene polymorphism has long been implicated to play a role in the pathogenesis of schizophrenia. Aim: In this study, we assessed the relationship of schizophrenia and its subgroups with 5-HT2A receptor gene polymorphism, and attempted to evaluate a possible correlation between the severity and prognosis of the illness and 5-HT2A receptor gene polymorphism. Method: Our study comprised 141 unrelated subjects who strictly met DSM-IV criteria for schizophrenia, and 79 healthy unrelated controls, all of Turkish origin. A clinical evaluation of all patients was accomplished applying the Brief Psychiatric Rating Scale (BPRS) test. The analysis of 5-HT2A receptor gene polymorphism was performed using the polymerase chain reaction technique. Results: Regarding 5-HT2A receptor gene polymorphisms, no statistically significant difference was found between schizophrenic patients and control subjects (p > 0.05). There was no significant difference between the average of BPRS points of the patients and 5-HT2A receptor gene polymorphisms (p > 0.05). Although there was no correlation between the duration of illness and polymorphism (p > 0.05), the frequency of hospitalization was found to be higher in the patients with T/C and T/T genotypes compared with the patients with C/C genotype (p < 0.05). Conclusion: Our findings indicate that the T102C polymorphisms of the 5-HT2A receptor gene does not play a substantial role in schizophrenia nor help evaluate susceptibility to schizophrenia. Since the 5-HT2A receptor gene polymorphism is associated with the frequency of hospitalization of the patients, it may be an indicator of prognosis in schizophrenia or help differentiate the patients who are somewhat refractory to antipsychotic treatment.

Long term and excessive use of 900 MHz radiofrequency radiation alter microRNA expression in brain

Abstract Purpose: We still do not have any information on the interaction between radiofrequency radiation (RF) and miRNA, which play paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. The purpose of this study was to bridge this gap by investigating effects of long-term 900 MHz mobile phone exposure on some of the miRNA in brain tissue. Materials and methods: The study was carried out on 14 Wistar Albino adult male rats by dividing them into two groups: Sham (n = 7) and exposure (n = 7). Rats in the exposure group were exposed to 900 MHz RF radiation for 3 h per day (7 days a week) for 12 months (one year). The same procedure was applied to the rats in the sham group except the generator was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106b-5p, rno-miR-107 and rno-miR-125a-3p in brain were investigated in detail. Results: Results revealed that long-term exposure of 900 MHz RF radiation only decreased rno-miR107 (adjP* = 0.045) value where the whole body (rms) SAR value was 0.0369 W/kg. However, our results indicated that other microRNA evaluated in this study was not altered by 900 MHz RF radiation. Conclusion: 900 MHz RF radiation can alter some of the miRNA, which, in turn, may lead to adverse effects. Therefore, further studies should be performed.

The A218C polymorphism of tryptophan hydroxylase gene and migraine

OBJECTIVE To determine the significance of the A218C polymorphism of the tryptophan hydroxylase (TPH) gene in migraine. METHODS Fifty-nine migraineurs and 62 healthy controls were included in the study, and polymerase chain reaction - restriction fragment length polymorphism assays were used to determine TPH A218C polymorphism. RESULTS There was no association between TPH gene polymorphism and gender, family history of migraine and epilepsy, or aura. There was no significant difference between the allele frequencies of both groups (p>0.05). A significant difference was found between the genotypes of the migraineurs and controls regarding the AA genotype. Homozygosity for the C allele or heterozygosity for the A or C was not associated with the occurrence of migraine (p>0.05), but homozygosity for the A allele was less frequent in the migraineurs (p=0.02). CONCLUSION Since it is unlikely that TPH polymorphism alters serotonin biosynthesis, its association with migraine may be attributed to linkage disequilibrium with a functional variant within the TPH gene or a nearby gene.

Monoamine oxidase-A gene promoter polymorphism in temporomandibular joint pain and dysfunction

Objective: In this study we aimed to evaluate the relationship between temporomandibular joint pain and dysfunction (TMJPD) within the frame of monoamine oxidase-A gene (MAO-LPR) gene polymorphism. Methods: Ninety-three patients with TMJPD, and 91 healthy volunteers were included in the study. Symptom Checklist-90-Revised (SCL-90-R), Montgomery-Asberg Depression Rating Scale (MADRS), and State and Trait Anxiety Inventory tests (STAI-I and STAI-II) were applied to the patients that were diagnosed as having TMJPD according to the standard clinical examination protocol. Blood samples were taken from the patients, and the variability in the MAO-A gene was analyzed by amplification of DNA with polymerase chain reaction (PCR) for a genetic association study. Results: The analysis of allele and genotype distribution for MAO-A gene polymorphism showed no significant differences between patients and controls. There was no significant association between the MAO-A polymorphism and psychiatric status of the male patients. However, the average of obsession and depression subscales scores (SCL 90-R) and MADRS points of the female patients who were homozygous for high activity alleles (2-2) were higher than those who were homozygous (1-1) and heterozygous (1-2) for low activitiy allele (f = 8.83, p< 0.01; f = 7.98, p< 0.01; f = 3.37, p = 0.04, respectively). Conclusion: This study does not provide evidence to support the involvement of MAOA gene in TMJPD. Our findings probably indicate that only the presence of the high activity alleles may play a role in the clinical symptomatology of TMJPD. Further studies are required to confirm our results as well as to understand the genetic basis of TMJPD. summary

N-Acetylcysteine Ameliorates γ-Radiation-Induced Deterioration of Bone Quality in the Rat Femur

This animal study evaluated the radioprotective effects of N-acetylcysteine (NAC) and amifostine on the biomechanical properties of bone in Wistar albino rats of both genders. The rats were randomly divided into four groups of eight: A control group (C); a group given a single dose of 40 Gy of g-irradiation (R); a group given γ-irradiation plus 200 mg/kg amifostine (R + amifostine); and a group given γ-irradiation plus 1000 mg/kg NAC (R + NAC). Extrinsic and intrinsic properties of bone, bone mineral density (BMD) and the cross-sectional area of the femoral shaft were determined. The cross-sectional area was significantly higher in the R + NAC and R + amifostine groups compared with the R and C groups. The BMD, maximum load and stiffness were also significantly higher in the R + NAC and R + amifostine groups than in the R group, and energy absorption capacity was higher in the R + NAC group than in the R group. These findings indicate that NAC and amifostine preserve bone quality in rats exposed to γ-irradiation.