RESUMO
CONTEXT: Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects. OBJECTIVE: We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I. DESIGN AND SETTING: Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used. PARTICIPANTS: For the final analyses, 3882 subjects aged 20-79 years were available. MAIN OUTCOME MEASURES: Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures. RESULTS: Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:-8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m(-2) by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (-2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels). CONCLUSION: We propose that the GH-IGF-I axis is a mediator for the relationship between FTO and BMI.
Assuntos
Índice de Massa Corporal , Hormônio do Crescimento Humano/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Obesidade/genética , Proteínas/genética , Adulto , Idoso , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Estudos Transversais , Feminino , Variação Genética , Genótipo , Alemanha , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Adulto JovemRESUMO
Wilson's disease (WD) is an autosomal-recessive inherited disorder of copper metabolism characterized by excessive deposition of copper throughout the body. If medical treatment fails in cases of fulminant hepatic failure and progressive hepatic dysfunction due to advanced cirrhosis, liver transplantation (OLTx) has been demonstrated to be a valuable treatment option. Between December 1993 and December 2002, 225 OLTxs in 198 patients were performed in our institution. In this consecutive series six patients (three females and three males) were liver grafted for WD. The follow-up ranged from 3 to 7 years. All patients are alive with well-functioning grafts at present. The ceruloplasmin levels increased after transplantation and remained normal. The Kayser-Fleischer ring disappeared in all patients, and urinary copper excretion normalized. The neurological manifestations in the two patients with severe neurological symptoms showed after 2 to 5 years a downward tendency; in one the ataxic movements disappeared completely. The psychiatric disorder in one patient disappeared as well the mild neurological symptoms in the patient with CHILD A cirrhosis. These two patients are fully recovered and returned to work. OLTx should be considered as a treatment option in patients with severe progressive neurological deficits even in cases with stable liver function since liver grafting definitely cures the underlying biochemical defect. In such cases an early decision for liver transplantation is justified because neurological deficits may become irreversible.
Assuntos
Degeneração Hepatolenticular/cirurgia , Transplante de Fígado/fisiologia , Cobre/metabolismo , Feminino , Degeneração Hepatolenticular/genética , Humanos , Transplante de Fígado/mortalidade , Masculino , Complicações Pós-Operatórias/classificação , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Fatores de TempoRESUMO
The risk of cluster headache (CH) is associated with the G-allele of the G1246A polymorphism in the hypocretin receptor 2 (HCRTR2) gene. First-line medication is effective in only about 70-80% of CH patients. We hypothesized that the HCRTR2 G1246A polymorphism is also of pharmacogenetic relevance in CH and may affect treatment response. We performed a prospective cohort study among 184 unrelated White CH patients. While the HCRTR2 1246G allele was significantly associated with CH in this group, treatment outcomes with triptans, oxygen, verapamil and corticosteroids remained unaffected. Our results do not support a role of the HCRTR2 G1246A polymorphism in drug responses in CH.
Assuntos
Analgésicos/uso terapêutico , Cefaleia Histamínica/tratamento farmacológico , Cefaleia Histamínica/genética , Avaliação de Resultados em Cuidados de Saúde/métodos , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas G/genética , Receptores de Neuropeptídeos/genética , Medição de Risco/métodos , Adulto , Cefaleia Histamínica/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Alemanha/epidemiologia , Humanos , Masculino , Receptores de Orexina , Prevalência , Prognóstico , Fatores de Risco , Resultado do TratamentoRESUMO
The G1246A polymorphism in the gene of the hypocretin receptor 2 (HCRTR2) has been linked to the risk for cluster headache (CH). The authors examined this association in a large sample of 226 patients with CH and 266 controls from Germany. The genotype and allele distribution varied significantly between patients and controls. Homozygous carriers of the G-allele had a twofold increase in risk for CH (OR 1.97; 95% CI 1.32 to 2.92; p = 0.0007).