RESUMEN
BACKGROUND: Currently, there is not any specific treatment for chronic pancreatitis (CP). It was aimed to investigate the effects of melatonin administration on endoplasmic reticulum (ER) stress, oxidative stress, fibrosis, biochemical and histopathological parameters, and Abcc2,Abcc5, and Abcg2 gene levels in an experimental rat CP model. METHODS: Forty rats were randomized into five groups: Sham, CP, CP+25 mg/kg melatonin, CP+50 mg/kg melatonin, and CP+placebo. In all rats, except the sham group, a model of chronic pancreatitis was accomplished with intraperitoneal caerulein administration. In treatment groups, melatonin was used as a therapeutic agent. Serum TGF-ß, TNF-α, MDA and GPx levels were studied. Pancreatic tissues were evaluated histopathologically. The expression levels of αSma,IR1α,Perk,Abcc2,Abcc5, and Abcg2 genes were measured with the qRT-PCR. RESULTS: Biochemical results of the melatonin groups exhibited favorable changes compared to the CP and placebo groups. αSma,IR1α,Perk expression levels were significantly lower in the melatonin groups. The expression levels of Abcc2, Abcc5, and Abcg2 were significantly higher in the CP group compared to the sham group, and these gene levels were significantly lower in the melatonin groups compared to the CP group (p < 0.01, p < 0.05, p < 0.05, respectively). DISCUSSION: In light of these favorable positive results, melatonin may be a useful preventive agent in the course of CP.
Asunto(s)
Melatonina , Pancreatitis Crónica , Ratas , Animales , Melatonina/farmacología , Melatonina/uso terapéutico , Pancreatitis Crónica/inducido químicamente , Pancreatitis Crónica/tratamiento farmacológico , Pancreatitis Crónica/prevención & control , Páncreas , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Estrés del Retículo EndoplásmicoRESUMEN
The glomerular tip lesion (GTL) is a distinctive histopathologic lesion which is regarded as a variant of focal and segmental glomerulosclerosis (FSGS). The prognostic significance of GTL among other FSGS variants has been disputed. In order to define the clinical features and outcome of GTL, we retrospectively reviewed the presenting clinical features, laboratory and biopsy findings and surveillance in our cohort of GTL, which consisted of 20 adults with native kidneys (mean age 46 years) with follow-up data ranging from 3 to 137 months. At presentation, mean urine protein, serum albumin and cholesterol levels were 5.17 g/d, 2.6 g/dL and 312.9 mg/dL, respectively, and none had renal insufficiency. Microscopic hematuria was detected in five patients. At biopsy, glomerular segmental lesions consisted of GTL without perihilar or collapsing lesions. GTL was observed in a variable proportion of glomeruli from 2.6% to 100%. Mesangial proliferation was seen in nine cases, at a moderate degree in two and mild in the rest. Three biopsies showed mild, two showed moderate interstitial fibrosis/tubular atrophy. Eleven patients received steroids alone and eight received sequential therapy with steroids and a cytotoxic agent. At a mean follow-up of 40.6 months, 17 patients (85%) achieved complete remission of nephrotic syndrome, 15% had partial remission. Four of 17 suffered from recurrences. No patient progressed to end-stage renal disease. Serum albumin at diagnosis was the only predictor of a recurrence (p = 0.037). Microscopic hematuria correlated with incomplete remission (p = 0.045). Our study demonstrates a clearly favorable prognosis in patients with FSGS-GTL variant.
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Citotoxinas/uso terapéutico , Glomeruloesclerosis Focal y Segmentaria/patología , Hematuria/tratamiento farmacológico , Glomérulos Renales/patología , Síndrome Nefrótico/tratamiento farmacológico , Proteinuria/tratamiento farmacológico , Esteroides/uso terapéutico , Adulto , Anciano , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Albúmina Sérica/análisis , Adulto JovenRESUMEN
We aimed to investigate the association between manganese superoxide dismutase (MnSOD) Ala-9-Val gene polymorphism and the initiation and/or progression of prostate cancer (PCa) as well as to evaluate its potential interactions with advanced age and smoking status. MnSOD Ala-9-Val gene polymorphism was carried out in 134 (mean age 64.1±7.48) PCa patients and 159 (mean age 62.5±7.53) healthy controls with serum prostate specific antigen (PSA) levels (<4 ng/ml) and normal digital rectal examination (DRE) findings in this prospectively designed study. PCa patients were classified as low stage disease (T1 or T2 and N0M0 stages) and high stage disease (T3 or T4 and N0M0 or N1 or M1 stages). Genotypes for MnSOD Ala-9-Val gene polymorphism were identified by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFPL). Despite lack of association between different genotypes of MnSOD Ala-9-Val gene polymorphism and the presence of PCa, patients with Ala/Ala genotype were at an increased risk of high stage disease compared with those with the Val/Val genotype [odds ratio (OR), 3.77; 95% CI, 1.30-10.94; P=0.012]. However, no significant difference was observed in the distribution of each genotype among PCa patients, with respect to tumor grade. On the other hand, smoking status and aging did not seem to change the association between genotypes and PCa risk. Ala/Ala genotype of MnSOD polymorphism may have an effect on adverse features of PCa such as high stage disease.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Neoplasias de la Próstata/enzimología , Fumar , Superóxido Dismutasa/genética , Factores de Edad , Anciano , Cartilla de ADN/genética , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Antígeno Prostático Específico/sangre , Estadísticas no Paramétricas , Encuestas y CuestionariosRESUMEN
PRIMARY OBJECTIVE: The present study was undertaken to evaluate whether enoant, which is rich in polyphenols, has any effect on electroencephalogram (EEG), oxidative stress and inflammation in ischemia/reperfusion (I/R) injury. METHODS: Ischemia was induced by 2-hour occlusion of bilateral common carotid artery. Animals orally received enoant. Group 1 was the ischemic control group. Group 2 was treated with enoant of 1.25 g kg⻹ per day for 15 days after I/R. Group 3 received the same concentration of enoant as in group 2 for 15 days before and after I/R. Group 4 was the sham operation group. EEG activities were recorded and the levels of TNF-α, IL-1ß and IL-6, TBARS and GSH were measured in the whole brain homogenate. RESULTS: There were significant changes in EEG activity in groups treated with enoant either before or after ischemia when compared with their basal EEG values. TNF-α, IL-6 and IL-1ß levels were significantly increased after I/R. GSH levels in group 3 treated with enoant in both pre- and post-ischemic periods were significantly increased and TBARS concentration was decreased compared with the ischemic group. CONCLUSION: The findings support that both pre-ischemic and post-ischemic administrations of enoant might produce neuroprotective action against cerebral ischemia.
Asunto(s)
Antioxidantes/farmacología , Bebidas , Isquemia Encefálica/tratamiento farmacológico , Electroencefalografía/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/tratamiento farmacológico , Vitis/química , Animales , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/prevención & control , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/fisiopatologíaRESUMEN
Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.
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Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/complicaciones , Homocisteína/sangre , Inflamación/sangre , Inflamación/complicaciones , Interleucina-2/sangre , Interleucina-6/sangre , Estudios de Casos y Controles , Demografía , Ácido Fólico/sangre , Humanos , Persona de Mediana Edad , Curva ROC , Vitamina B 12/sangreRESUMEN
Interleukin-15 (IL-15) is a potent proinflammatory cytokine that is now considered a key component of atherosclerosis. Proinflammatory gene polymorphisms lead to variations in the production and level of the proteins. In light of these findings, we hypothesized that variations in the gene coding for IL-15 influence the risk of coronary heart disease (CHD) by modulating the IL-15 levels. To test this hypothesis, we examined 5 single nucleotide polymorphisms (SNPs) in IL-15 gene and IL-15 levels in 102 patients with acute coronary syndrome (ACS), 102 patients with chronic ischemic stable CHD and 162 healthy control subjects. This study is the first report showing the influences of IL-15 gene variants and IL-15 levels on CHD. The five single nucleotide polymorphisms (SNPs) within the IL-15 gene, G367A, C267T, A14035T, C13687A, and A10504G were carried out by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Serum IL-15 levels were significantly higher in both acute and chronic patients than in controls. Genetic variants of IL-15 gene and IL-15 levels were associated with CHD. In conclusion, our study supports the hypothesis that genetic variation in IL-15 gene and IL-15 levels influence the risk of CHD. Further studies are needed to confirm our hypothesis.
Asunto(s)
Enfermedad Coronaria , Interleucina-15 , Polimorfismo de Nucleótido Simple , Anciano , Enfermedad Coronaria/sangre , Enfermedad Coronaria/genética , Enfermedad Coronaria/inmunología , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Interleucina-15/sangre , Interleucina-15/genética , Persona de Mediana Edad , Datos de Secuencia Molecular , Factores de RiesgoRESUMEN
We examined whether the GRIK3 (T928G) polymorphic variants in patients with schizophrenia are different from those of their first-degree relatives and healthy controls. The study population was composed of 256 patients with schizophrenia, 305 first-degree relatives of schizophrenia patients and 242 healthy control subjects. The GRIK3 (T928G) polymorphism was determined by restriction fragment length polymorphism. The frequency of the TT genotype was predominant, whereas the GG genotype was rare among all groups. The frequencies of GRIK3 (T928G) genotype distributions in the patients with schizophrenia were similar to those of their relatives. The frequency of the GG genotype was significantly higher in patients than in healthy controls. Similarly, GG genotype distribution in relatives was elevated compared with that in controls, but this value did not reach statistical significance. On the other hand, the subgroups of schizophrenia patients did not show a significant association with the GRIK3 (T928G) gene. It appears that the patients share the same (GRIK3) T928G gene variants with their relatives. One interpretation of our findings is that the relatives are at risk for the development of schizophrenia in the future.
Asunto(s)
Salud de la Familia , Familia , Predisposición Genética a la Enfermedad , Polimorfismo de Longitud del Fragmento de Restricción/genética , Receptores de Ácido Kaínico/genética , Esquizofrenia/genética , Adulto , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Receptor Kainato GluK3RESUMEN
BACKGROUND: The aim of the present study was to investigate the association between genetic variants in metylenetetrahydrofolate reductase (MTHFR) and Paraoxonase-1 (PON1) 55/192 genes and total homocysteine (tHcy), folate, B12 vitamin, and PON1 levels in patients with coronary artery disease (CAD). METHODS: The study included 235 patients with CAD and 268 healthy control subjects. RESULTS: LL and LM genotypes and L allele of PON1 55 were over-represented in patients. In contrast, MM genotype and M allele were more frequent in controls. QQ genotype and Q allele of PON1 192 and CT genotype of MTHFR were significantly diminished and QR genotype and R allele were significantly elevated in CAD patients compared with controls. The plasma tHcy were elevated but B12 levels were diminished in patients. PON1 55 and 192 genetic variants were significantly associated with PON1 activity, triglyceride, total cholesterol, tHcy and, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol in patients, respectively. CONCLUSION: Genetic variants of PON1 55/192 and MTHFR were associated with CAD.
Asunto(s)
Arildialquilfosfatasa/genética , Enfermedad de la Arteria Coronaria/metabolismo , Ácido Fólico/metabolismo , Homocisteína/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Vitamina B 12/metabolismo , Anciano , Enfermedad de la Arteria Coronaria/enzimología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
There is growing evidence of partial etiological overlap between schizophrenia (SZ) and bipolar I disorder (BD-I) from linkage analysis, genetic epidemiology and molecular genetics studies. SZ and BD-I are neurodevelopmental disorders with genetic and environmental etiologies. Recent studies have demonstrated that matrix metalloproteinase 3 (MMP3) is a key event in associative memory formation, learning and synaptic plasticity, which are important in psychiatric disorders. In the light of these findings, we analyzed the genetic variations in the MMP3-1171 5A/6A in patients with SZ, patients with BD-I and healthy controls. To the best of our knowledge, this is the first study to report an association of variation in gene encoding MMP3 with SZ. Our study group consisted of 111 unrelated patients with SZ, 141 unrelated patients with BD-I, and 121 unrelated healthy controls. The frequencies of 6A6A genotype and 6A allele distributions of MMP3 in patients with SZ were significantly decreased when compared with controls. In contrast, in patients with SZ, the distributions of 5A5A genotype and 5A allele of MMP3 gene were significantly increased as compared with healthy controls. When the frequencies of genotypes or alleles in schizophrenic patients and bipolar patients were compared, 6A6A genotype and 6A allele in patients with BD-I were significantly higher than patients with SZ. In contrast, 5A5A genotype and 5A allele distributions of MMP3 gene were significantly frequent in patients with SZ. On the other hand, no significant differences were found in the allele or genotype distribution in patients with BD-I compared with controls. In conclusion, our data have supported the hypothesis that there is a possible relationship between -1171 5A/6A polymorphism of MMP3 gene and SZ. A larger sample group is needed to confirm the potential role of this gene in the pathophysiology of psychiatric disorders.
Asunto(s)
Trastorno Bipolar/genética , Predisposición Genética a la Enfermedad/genética , Metaloproteinasa 3 de la Matriz/genética , Polimorfismo de Nucleótido Simple/genética , Esquizofrenia/genética , Adulto , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Ligamiento Genético , Humanos , Masculino , Persona de Mediana Edad , Escalas de Valoración PsiquiátricaRESUMEN
We investigated the effect of polymorphic variants of c.1298A>C (Glu429Ala) and c.677C>T (Ala222Val) in methylenetetrahydrofolate (MTHFR) gene on the total homocysteine (tHcy), folate and B12 levels in patients with bipolar disorder, first-degree relatives of patients, and controls. The c.677C>T and c.1298A>C polymorphisms in MTHFR were determined by polymerase chain reaction-restriction fragment length polymorphism in 197 bipolar patients, 278 relatives and 238 controls. tHcy and folate and vitamin B12 levels were measured by Fluorescence Polarization Immunoassay and Electrochemiluminescence, respectively. The tHcy was significantly increased in patients and relatives. In contrast, folate and B12 were significantly lower in patients and relatives. Gender was not considered as a significant determinant in the multivariate analysis. Genotypes of c.1298A>C and c.677C>T were correlated with tHcy, folate and B12. Patients and relatives carrying TT and/or AA and AC genotypes had elevated tHcy and reduced folate and B12 levels. High tHcy but low folate and vitamin B12 levels may be a risk factor for development of bipolar disorder.
Asunto(s)
Trastorno Bipolar/sangre , Trastorno Bipolar/genética , Familia , Ácido Fólico/sangre , Homocistina/sangre , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Vitamina B 12/sangre , Adulto , Análisis de Varianza , Femenino , Inmunoensayo de Polarización Fluorescente/métodos , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: We investigated the association of matrix metalloproteinase-3 (MMP-3) and paraoxonase 1 (PON1) 55/192 polymorphisms with coronary artery disease (CAD) and the number of diseased vessels in patients with CAD. MATERIAL/METHODS: One hundred thirty-nine CAD patients and 119 healthy control subjects were included in the study. Genotypes for PON1 55/192 and MMP-3 5A/6A polymorphisms were determined by restriction fragment length polymorphism. RESULTS: Although distributions of the RR genotype of PON1 192 and the 5A5A genotype of MMP-3 were more frequent in patients, frequencies of the QQ genotype of PON1 192, the MM genotype of PON1 55, and the 6A6A genotype of MMP-3 were significantly lower in patients compared with healthy control subjects. The combined genotypes of RR/LL and/or 5A5A are increased the risk of CAD when compared with subjects who possess neither the MMP-3 5A5A nor the PON1 RR/LL genotype. While the MMP-3 5A/6A genetic variants were not associated with the number of diseased vessels, PON1 55/192 variants were associated with the number of diseased vessels. CONCLUSIONS: The combined PON1 55/192 and MMP-3 5A/6A genetic variants are associated with CAD; PON1 seems to be connected with the number of diseased vessels, and hypertension and hyperlipidemia are related with PON1 192 and MMP-3 in CAD patients.
Asunto(s)
Arildialquilfosfatasa/genética , Enfermedad de la Arteria Coronaria/genética , Metaloproteinasa 3 de la Matriz/genética , Polimorfismo Genético , Adulto , Anciano , Alelos , Enfermedad de la Arteria Coronaria/patología , Diabetes Mellitus/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Hiperlipidemias/genética , Hipertensión/genética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/genética , Polimorfismo de Longitud del Fragmento de Restricción , TurquíaRESUMEN
OBJECTIVES: We aimed to evaluate the relationship between interleukin-8 and the oxidant-antioxidant system in end-stage renal failure patients with and without diabetes mellitus undergoing regular hemodialysis treatment. MATERIALS AND METHODS: Plasma levels of malondialdehyde and whole blood reduced glutathione were measured as markers of the oxidant and antioxidant systems, respectively. Plasma interleukin-8 levels were measured by enzyme-linked immunosorbent assay. RESULTS: When compared with controls, plasma interleukin-8 levels were elevated in both diabetic and nondiabetic end-stage renal disease patients. Plasma malondialdehyde levels were statistically significantly higher in end-stage renal disease patients with and without diabetes mellitus than they were in controls; however, reduced glutathione levels were statistically significantly lower in diabetic and nondiabetic end-stage renal disease patients than they were controls. CONCLUSIONS: In end-stage renal disease patients with and without diabetes mellitus, elevated interleukin- 8 levels and decreased reduced glutathione levels may be attributed to increased oxidative stress due to inflammation. In other words, increased reactive oxygen species may induce interleukin-8 production and result in diminished reduced glutathione levels. Our data suggest a relationship between interleukin- 8 and the oxidant-antioxidant system in end-stage renal failure patients.
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Antioxidantes/metabolismo , Interleucina-8/sangre , Fallo Renal Crónico/metabolismo , Oxidantes/metabolismo , Adulto , Nefropatías Diabéticas/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Glutatión/sangre , Humanos , Fallo Renal Crónico/sangre , Masculino , Malondialdehído/sangre , Persona de Mediana EdadRESUMEN
PURPOSE: We aimed to investigate the exact localization of neural pathway and the frequency of nerve fibers, which are located in the pelvic facial layers in the prostate and periprostatic regions. MATERIALS AND METHODS: We used four fresh frozen cadavers in this trial. Anatomical layers of anterior rectus fascia and abdominal rectus muscle were dissected to reach the retropubic area. Prostate, visceral and parietal pelvic fascia, levator ani muscle and puboprostatic ligaments were identified. Nine tissue samples, each 1x1 cm in size, were obtained from each cadaver and grouped separately. The locations of these samples are as follows. Group G I from 12 o'clock (apical region), G II from right prostatic apex, G III from 2 o'clock, G IV from right far pelvic lateral, G V from 5 o'clock, G VI from 7 o'clock, GVII from left far pelvic lateral, G VIII from 10 o'clock and G IX from left prostatic apex. Nerve distribution, frequency and diameters of these 9 groups were compared to each other. RESULTS: 36 specimens were obtained from 4 cadavers. Mean number of nerve fibers was 14.1. The number of nerve fibers in each location were not statistically different from each other (P = .9). Mean nerve diameter was 89.1 µm. Mean diameter of nerves was statistically different between groups II, III IV and VI and VIII (P = .001). No difference was seen amongst others. CONCLUSION: The distributions of nerve fibers at prostate and peri-prostatic region were homogeneous while the nerve diameters varied amongst the different regions.
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Fascia/anatomía & histología , Plexo Hipogástrico/anatomía & histología , Próstata/inervación , Puntos Anatómicos de Referencia , Cadáver , Disección , Humanos , MasculinoRESUMEN
Adenomyosis that is a form of endometriosis is the growth of ectopic endometrial tissue within the muscular wall of the uterus (myometrium), which may cause dysmenorrhea and infertility. Endocannabinoid mediated apoptotic mechanisms of endometriosis and adenomyosis are not known. We hypothesized that the down regulation of endocannabinoid receptors and/or alteration in their regulatory enzymes may have a direct role in the pathogenesis of endometriosis and adenomyosis through apoptosis. Endocannabinoid receptors CB1 and CB2, their synthesizing and catabolizing enzymes (FAAH, NAPE-PLD, DAGL, MAGL) and the apoptotic indexes were immunohistochemically assessed in endometriotic and adenomyotic tissues. Findings were compared to normal endometrium and myometrium. Endometrial adenocarcinoma (Ishikawa) and ovarian endometriosis cyst wall stromal (CRL-7566) cell lines were furthermore cultured with or without cannabinoid receptor agonists. The IC50 value for CB1 and CB2 receptor agonists was quantified. Cannabinoid agonists on cell death were investigated by Annexin-V/Propidium iodide labeling with flow cytometry. CB1 and CB2 receptor levels decreased in endometriotic and adenomyotic tissues compared to the control group (p=0,001 and p=0,001). FAAH, NAPE-PLD, MAGL and DAGL enzyme levels decreased in endometriotic and adenomyotic tissues compared to control (p=0,001, p=0,001, p=0,001 and p=0,002 respectively). Apoptotic cell indexes both in endometriotic and adenomyotic tissues also decreased significantly, compared to the control group (p=0,001 and p=0,001). CB1 and CB2 receptor agonist mediated dose dependent fast anti-proliferative and pro-apoptotic effects were detected in Ishikawa and ovarian endometriosis cyst wall stromal cell lines (CRL-7566). Endocannabinoids are suggested to increase apoptosis mechanisms in endometriosis and adenomyosis. CB1 and CB2 antagonists can be considered as potential medical therapeutic agents for endometriosis and adenomyosis.
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Adenomiosis/fisiopatología , Apoptosis/fisiología , Endocannabinoides/metabolismo , Endometriosis/fisiopatología , Apoptosis/efectos de los fármacos , Agonistas de Receptores de Cannabinoides/farmacología , Antagonistas de Receptores de Cannabinoides/farmacología , Línea Celular , Femenino , Citometría de Flujo , Humanos , Concentración 50 Inhibidora , Unión Proteica/efectos de los fármacos , Receptor Cannabinoide CB1/agonistas , Receptor Cannabinoide CB1/antagonistas & inhibidores , Receptor Cannabinoide CB2/agonistas , Receptor Cannabinoide CB2/antagonistas & inhibidoresRESUMEN
AIMS: Migraine is a common and debilitating episodic disorder characterized by recurrent headache attacks associated with autonomic symptoms. It affects an estimated 12% of the population. The etiology of the underlying neurodegenerative process is widely unknown; however, oxidative stress is a unifying factor in the current theories of migraine pathogenesis. After demonstrating the observation that oxidative DNA damage is detectable in migraine disease, searching the role played by DNA repair systems in migraine diseases could bring us much significant information about the pathogenesis of migraine. We prospectively investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) account for an increased risk of migraine. The present analyses are based on 135 case subjects with migraine disease and 101 noncase subjects. Genotyping of DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, hOGG1 Ser326Cys) was detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We demonstrated that apurinic endonuclease (APE), X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3), xeroderma pigmentosum D (XPD), and hOGG1 gene variants were associated with an increased risk for development of migraine disease (p<0.05). In contrast, no statistically significant differences were found in genotype distributions of X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) and XPG between migraine cases and controls (p>0.05). CONCLUSIONS: Our findings have suggested that APE1, XRCC3, XPD, and hOGG1 gene variants could facilitate the development of migraine disease.
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ADN Glicosilasas/genética , Reparación del ADN/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Proteínas de Unión al ADN/genética , Trastornos Migrañosos/genética , Polimorfismo Genético , Proteína de la Xerodermia Pigmentosa del Grupo D/genética , Adulto , Animales , Cricetinae , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: Migraine is a multifactorial and complex disorder, and any clear diagnostic marker to assess the status of the migraineurs has not been established, yet. Nonsteroidal anti-inflammatory drugs reduce production of prostanoids including PGE2 by inhibiting COX-1 and/or COX-2, and thereby suppress inflammatory pain in patients suffering from rheumatoid arthritis, osteoarthritis, and migraine. Thus, COX-2 regulation is important in the pathogenesis and treatment of migraine. We prospectively investigated COX-2-765GâC and COX-2-1195AâG gene polymorphisms which may account for an increased risk of migraine. METHODS: The present analyses are based on 144 case subjects with migraine disease and 123 non-case subjects. Genotyping of COX-2 gene polymorphisms (COX-2-765GâC, COX-2-1195AâG) was detected by PCR-RFLP. RESULTS: We, for the first time, demonstrated positive association of COX-2 gene variants with an increased risk for development of migraine. Carriers of COX-2-765 C+ genotype in controls were higher than in the patients (57.7% and 36.1% respectively; P<0.0001) and the frequencies of G+ genotype in patients were higher than in the controls (97.9% and 88.6% respectively; P: 0.002). In addition, frequencies of COX-2-765 GG and GC genotypes in patients were higher than in the controls (P<0.0001, P<0.0001 respectively). It seems that COX-2-765 G+ genotype had increased and COX-2-765 C+ genotype had decreased risk for migraine. In COX-2-1195 polymorphism only AG genotype was statistically significantly different in patients than in the controls (P<0.05). CONCLUSIONS: Our findings have suggested that COX-2-765 G+ genotype could facilitate the development of migraine disease.
Asunto(s)
Ciclooxigenasa 2/genética , Predisposición Genética a la Enfermedad , Trastornos Migrañosos/genética , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Adulto JovenRESUMEN
BACKGROUND: Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk. METHODS: We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls. RESULTS: We found significant associations in the analyses of CHEK2- 1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2- Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (?2=7.655; p=0.0057) in the patient group compared to controls. CONCLUSION: In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.
Asunto(s)
Proteína BRCA2/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Quinasa de Punto de Control 2/genética , Haplotipos/genética , Mutación/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , TurquíaRESUMEN
Obsessive compulsive disorder is a common psychiatric disorder defined by the presence of obsessive thoughts and repetitive compulsive actions. The mutations or polymorphic variants in mitochondrial DNA-encoded genes or nuclear genes result in oxidative stress, which has recently been associated with various psychiatric disorders. In order to understand the association of mitochondrial disorders with oxidative stress in obsessive compulsive disorder, we examined genetic variants of manganese superoxide dismutase and uncouple-2 antioxidant genes and malondialdehyde and glutathione, markers of oxidative stress. The study sample comprised 104 patients with OCD and 110 healthy controls. For manganese superoxide dismutase, the frequencies of CT (Ala/Val) genotype (p < 0.01) in patients were significantly lower than those of controls. In contrast, CC (Ala/Ala) genotype was significantly more frequent in patients than controls (p < 0.05). For uncouple-2 I/D, the frequencies of ID genotype (p < 0.01) and I allele (p < 0.05) were lower in patients as compared with controls. In contrast, DD genotype was more prevalent in patients than controls (p < 0.01). While whole blood glutathione was significantly diminished (p < 0.0001), serum malondialdehyde was significantly elevated in patients compared with controls (p < 0.0001). Malondialdehyde levels were significantly elevated in subjects with DD genotype of UCP-2 I/D (p < 0.05) and CC genotype of manganese superoxide dismutase (p < 0.05) as compared with II or ID and TT or CT genotype, respectively. Malondialdehyde levels in patients carrying CC (p < 0.05) or CT (p < 0.05) genotype were significantly higher than those of carrying TT genotype. In conclusion, CC genotype of manganese superoxide dismutase or DD genotype of UCP-2 might result in mitochondrial disorders by increasing oxidative stress in obsessive compulsive disorders.
Asunto(s)
Canales Iónicos/genética , Proteínas Mitocondriales/genética , Trastorno Obsesivo Compulsivo/fisiopatología , Estrés Oxidativo/genética , Polimorfismo de Nucleótido Simple/genética , Superóxido Dismutasa/genética , Adulto , Femenino , Genotipo , Glutatión/sangre , Humanos , Desequilibrio de Ligamiento , Peroxidación de Lípido/genética , Modelos Logísticos , Masculino , Malondialdehído , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/genética , Oportunidad Relativa , Estudios Retrospectivos , Proteína Desacopladora 2RESUMEN
AIMS: There is a growing interest in the understanding of a possible role of DNA repair systems in ageing and neurodegenerative diseases after DNA damage is observed in the brain of individuals affected by neurodegenerative diseases. In the light of these findings, we investigated whether DNA repair gene polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met XPD Lys751Gln, XPG Asp1104His, APE1 Asp148Glu, and HOGG1 Ser326Cys) account for an increased risk of Parkinson's disease (PD). METHODS: The present analyses are based on 60 case subjects with PD and 108 unrelated healthy controls. Genotyping of DNA repair gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We, for the first time, demonstrated the positive association of APE1, XRCC1, and XRCC3 DNA repair gene variants with PD risk. In our study, the frequencies of Glu/Glu genotype in APE1, Gln+ genotype of XRCC1, and Thr+ genotype of XRCC3 are higher in patients than in controls (p=0.028, p=0.002 and p=0.046, respectively). CONCLUSIONS: In conclusion, our findings have suggested that APE1, XRCC1, and XRCC3 genetic variants may be a risk factor by increasing oxidative stress that might cause the loss of dopaminergic cells in the substantiata nigra and locus caeruleus, leading to abnormal signal transmittion, and ultimately, the development of PD. In addition, generation of reactive oxygen species from dopamine might affect the other DNA repair pathway proteins that we did not examine in the current study. Further studies with larger sample groups are necessary to clarify the role of DNA repair genes and the development of PD.
Asunto(s)
Reparación del ADN/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Proteínas de Unión al ADN/genética , Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/genética , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos XRESUMEN
BACKGROUND: Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including schizophrenia (SZ) and bipolar disorders (BDs). As SZ and BD have some susceptibility genes in common and since unaffected first-degree relatives of these patients carry a high likelihood of these susceptibility genes, we aimed to elucidate the role of angiotensin-converting enzyme (ACE) genetic variants in patients with SZ, BD and their first-degree relatives. METHODS: The study sample comprised 239 patients with SZ, 184 patients with BD, 284 unaffected first-degree biological relatives of patients with SZ and 301 unaffected first-degree biological relatives of patients with BD and 210 healthy controls. The ACE genotypes were determined by polymerase chain reaction. RESULTS: ACE insertion/deletion polymorphism was associated with SZ and BD. DD genotype and D allele distributions in bipolar patients and their first-degree relatives were significantly higher than those of SZ patients, their relatives, and controls. In contrast, II genotype and I allele were reduced in both the patient groups and their relatives as compared with controls. CONCLUSION: In this study, the D allele might be responsible for clustering of psychotic symptoms and results in the psychotic manifestations of BD, whereas I allele seems to be protective against development of SZ and BD. SZ and BD characterized by similar or different gene variant in ACE could be a useful marker for these psychiatric disorders, if this polymorphism is replicated in the future studies.