RESUMO
We hypothesized that the IL-1ß-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1ß-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1ß-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1ß-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits.
Assuntos
Antineoplásicos/efeitos adversos , Predisposição Genética para Doença , Homozigoto , Interleucina-1beta/genética , Síndromes Neurotóxicas/genética , Polimorfismo de Nucleotídeo Único , Antineoplásicos/uso terapêutico , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Testes NeuropsicológicosRESUMO
BACKGROUND AND PURPOSE: Frontotemporal lobar degeneration (FTLD) is considered as a proteinopathy; therefore, it is conceivable that genes encoding for factors involved in protein misfolding and/or degradation could play a role in its pathogenesis. METHODS: An association study of defective in cullin neddylation 1 (DCN-1)-domain containing 1 (DCUN1D1), which is involved in protein degradation, was carried out in a population of 220 patients with FTLD as compared with 229 age-matched controls. RESULTS: A statistically significant increased frequency of the GG genotype of the DCUN1D1 rs4859146 single nucleotide polymorphism (SNP) was observed in patients compared with controls (6.9 vs. 1.7%, P = 0.011, adjusted OR: 4.39, 95% CI: 1.40-13.78). Stratifying according to the clinical syndrome, significant differences were observed between the behavioral variant of frontotemporal dementia and controls (GG frequency: 6.3 vs. 1.7%, P = 0.02, OR:4.0, 95%, CI = 1.24-12.92), as well as between patients with progressive aphasia compared with controls (15.4 vs. 1.7%, P = 0.014, OR = 11.30, 95%, CI = 1.63-78.45), but not in patients with SD versus controls (8.3 vs. 1.7%, P = 0.18, OR = 5.24, 95% C.I. = 0.45-60.63). No significant differences in allelic and genotypic frequencies of the DCUN1D1 rs4859147 SNP were found. CONCLUSIONS: The GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold.
Assuntos
Demência/etiologia , Demência/genética , Predisposição Genética para Doença , Proteínas Oncogênicas/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Análise Mutacional de DNA/métodos , Éxons/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Proteínas , Proteínas Proto-Oncogênicas , Fatores de RiscoRESUMO
Aquaporin4 (AQP4) has an important role in water homeostasis of human brain and a dysfunction of AQP4 could induce pathological conditions in neuronal activity. The purpose of our work was to evaluate the association of polymorphisms in the AQP4 gene with the risk and the clinical features of migraine. A total of 293 migraineurs and 249 controls were involved in the study. They were genotyped for four single nucleotide polymorphisms (SNPs) of AQP4 gene. No significant difference in the distribution of AQP4 genotypic and allelic frequencies between cases and controls was found. In addition, haplotype analysis did not show any significant difference. Comparison of the clinical features of the disease according to different AQP4 genotypes showed no significant difference. Our data do not support the hypothesis that the AQP4 gene could represent a genetic susceptibility factor for migraine.
Assuntos
Aquaporina 4/genética , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND AND AIMS: Neuronal nitric oxide synthase (NOS)1 C276T polymorphism was shown to increase the risk for frontotemporal lobar degeneration (FTLD). In the brain, both NOS1 and NOS3 (endothelial isoform) have been detected. The distribution of NOS3 G894T (Glu298Asp) and T-786C single nucleotide polymorphisms (SNPs) was analyzed in a population of 222 patients with FTLD compared with 218 age-matched controls to determine whether they could influence the susceptibility to develop the disease. RESULTS: A statistically significant increased frequency of the NOS3 G894T SNP was observed in patients as compared with controls (40.0 vs. 31.4%, P = 0.011, OR: 1.65, CI: 1.13-2.42). Conversely, the distribution of the T-786C SNP was similar in patients and controls. No differences were observed stratifying according to gender. DISCUSSION: The NOS3 G894T polymorphism likely acts as risk factor for sporadic FTLD, but studies in larger populations are needed to confirm these preliminary findings.
Assuntos
Degeneração Lobar Frontotemporal/enzimologia , Degeneração Lobar Frontotemporal/genética , Predisposição Genética para Doença/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Degeneração Lobar Frontotemporal/epidemiologia , Predisposição Genética para Doença/epidemiologia , Testes Genéticos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/deficiência , Gravidez , Fatores de RiscoRESUMO
OBJECTIVE: Several lines of evidence indicate a role for inflammatory processes in the development of cerebral aneurysms. Recently, polymorphisms in the promoter region of the interleukin 6 (IL6) gene were shown to be associated with intracranial aneurysmal disease. The purpose of this study was to verify the association of two functionally active polymorphisms (-174 G>C and -572 G>C) in the promoter region of the IL6 gene with the risk and clinical features of aneurysmal subarachnoid haemorrhage (SAH) in an Italian population. METHODS: A total of 179 consecutive aneurysmal SAH patients and 156 healthy controls were involved in the study. Cases and controls were genotyped for the -174 GAssuntos
Genética Populacional
, Interleucina-6/genética
, Aneurisma Intracraniano/genética
, Polimorfismo Genético/genética
, Regiões Promotoras Genéticas/genética
, Hemorragia Subaracnóidea/genética
, Adulto
, Idoso
, Feminino
, Frequência do Gene
, Predisposição Genética para Doença/genética
, Genótipo
, Haplótipos
, Humanos
, Itália
, Masculino
, Pessoa de Meia-Idade
, Fatores de Risco
RESUMO
Studies in experimental animals have suggested that the hypocretin/orexin system may be involved in migraine pathophysiology. Using a case-control design study, we genotyped 246 migraine patients and 239 healthy controls for the 1246G-->A polymorphism of the hypocretin receptor 2 (HCRTR2) gene. Genotypic and allelic frequencies of the examined polymorphism were similarly distributed between cases and controls (chi2 = 2.22, P = 0.14 and chi2 = 2.45, P = 0.29, respectively). When different migraine subgroups were compared (migraine with aura vs. migraine without aura and episodic vs. chronic migraine) no significant difference was found. Comparison of the clinical features of the disease with the 1246G-->A genotypes showed no significant difference. Our data suggest that the HCRTR2 gene is not a genetic risk factor in migraine.
Assuntos
Predisposição Genética para Doença , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Receptores de Orexina , Reação em Cadeia da PolimeraseRESUMO
Several studies have suggested that iron metabolism may be involved in the pathogenesis of migraine. Using a case-control design, we performed an association study in a cohort of Italian migraine patients to evaluate whether a particular allele or genotype of the haemochromatosis gene (HFE) would modify the occurrence and clinical features of the disease. We genotyped 256 migraine patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y and H63D polymorphisms of the HFE gene. Phenotype and allele frequencies of both polymorphisms were similarly distributed in migraine patients and controls. The patients carrying the DD genotype of the H63D polymorphism showed a later age at onset of the disease and an increased number of migraine attacks. Our data suggest that the HFE gene is not a major disease gene for migraine. However, the H63D polymorphism of the HFE gene may be considered a modifying genetic factor in migraine.
Assuntos
Testes Genéticos/métodos , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana/genética , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/genética , Polimorfismo de Nucleotídeo Único/genética , Medição de Risco/métodos , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Análise Mutacional de DNA/métodos , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Proteína da Hemocromatose , Heterozigoto , Humanos , Incidência , Itália/epidemiologia , Masculino , Fatores de RiscoRESUMO
Recent studies suggested that genetic factors play a role in cluster headache (CH). However, the type and the number of genes involved in the disease are still unclear. We performed an association study in a cohort of Italian CH patients to evaluate whether a particular allele or genotype of the Clock gene would modify the occurrence and the clinical features of the disease. One hundred and seven CH patients, diagnosed according to the International Classification of Headache Disorders, 2nd Edition, (ICHD-II) criteria, and 210 healthy age, sex and ethnicity-matched controls were genotyped for the 3092 T-->C Clock gene polymorphism (also known as 3111 T-->C). Phenotype and allele frequencies were similarly distributed in CH patients and controls. The clinical features of the disease were not significantly influenced by different genotypes. In conclusion, our study suggests that the 3092 T-->C polymorphism of the Clock gene is unlikely to play an important role in cluster headache.
Assuntos
Cefaleia Histamínica/genética , Polimorfismo de Nucleotídeo Único/genética , Transativadores/genética , Adulto , Proteínas CLOCK , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Fenótipo , Reação em Cadeia da PolimeraseRESUMO
Several polymorphisms of the hypocretin/orexin system genes were evaluated in 109 cluster headache patients and 211 controls. The 1246 G>A polymorphism of the gene was significantly different between cases and controls. Homozygosity for the G allele was associated with an increased disease risk (OR: 6.79, 95% CI, 2.25 to 22.99). The data suggest that the HCRTR2 gene or a linked locus significantly modulates the risk for cluster headache.
Assuntos
Cefaleia Histamínica/genética , Receptores de Neuropeptídeos/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Orexina , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas GRESUMO
OBJECTIVES: The risk of uniparental disomy (UPD) occurrence associated with the prenatal finding of balanced nonhomologous Robertsonian translocations (NHRTs) has been estimated only on limited empirical data. The aim of the study was to verify the estimate of the general risk, to get narrower confidence intervals by cumulating the data and to obtain risk estimates for specific translocation types. METHODS: We tested for UPD 160 prenatal specimens referred to the participant centers after the cytogenetic finding of NHRT. RESULTS: One case of upd(14)mat was found, associated with a 45,XX,der(14;22)mat fetal karyotype. The general empirical risk of UPD occurrence in NHRT carrier fetuses, corrected for the actual number of chromosomes analyzed, was 0.76% (95% CI 0.02-4.25%). Cumulative data with previous studies gives a general risk of UPD associated with NHRT of 0.80% (95% CI 0.17-2.34%). The UPD risk for the specific NHRT der(13;14) did not significantly differ from that of the other NHRTs taken together. CONCLUSION: The present survey confirms the previously estimated risk of occurrence of UPD in offspring of NHRT carriers as a low, but not negligible risk, worth being investigated in prenatal diagnosis.
