RESUMO
OBJECTIVE: Normosmic idiopathic hypogonadotropic hypogonadism (nIHH) is characterized by failure of initiation or maintenance of puberty due to insufficient gonadotropin release, which is not associated with anosmia/hyposmia. The objective of this study was to determine the distribution of causative mutations in a hereditary form of nIHH. METHODS: In this prospective collaborative study, 22 families with more than one affected individual (i.e. multiplex families) with nIHH were recruited and screened for genes known or suspected to be strong candidates for nIHH. RESULTS: Mutations were identified in five genes (GNRHR, TACR3, TAC3, KISS1R, and KISS1) in 77% of families with autosomal recessively inherited nIHH. GNRHR and TACR3 mutations were the most common two causative mutations occurring with about equal frequency. CONCLUSIONS: Mutations in these five genes account for about three quarters of the causative mutations in nIHH families with more than one affected individual. This frequency is significantly greater than the previously reported rates in all inclusive (familial plus sporadic) cohorts. GNRHR and TACR3 should be the first two genes to be screened for diagnostic purposes. Identification of causative mutations in the remaining families will shed light on the regulation of puberty.
Assuntos
Saúde da Família , Hipogonadismo/genética , Mutação , Receptores LHRH/genética , Receptores da Neurocinina-3/genética , Adolescente , Adulto , Estudos de Coortes , Estudos de Associação Genética , Humanos , Hipogonadismo/congênito , Hipogonadismo/metabolismo , Lactente , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Neurocinina B/genética , Neurocinina B/metabolismo , Estudos Prospectivos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Kisspeptina-1 , Receptores LHRH/metabolismo , Receptores da Neurocinina-3/metabolismo , Taquicininas/genética , Taquicininas/metabolismo , Turquia , Adulto JovemRESUMO
INTRODUCTION: Plasma carnitine insufficiency has been known to cause muscle weakness. Carnitine levels and pulmonary functions were lower in patients with diabetes. PATIENTS AND METHODS: To determine whether pulmonary functions are correlated with carnitine levels in patients with type 2 diabetes. In this study, we evaluated pulmonary functions and carnitine concentrations in 49 patients with type 2 diabetes and 34 healthy controls. RESULTS: Carnitine levels were lower in type 2 diabetes group than control group (52.56 +/- 12.38 and 78.96 +/- 10.66 hmol/mL, respectively, p < 0.0001). Pulmonary functions were not significantly different between groups. Carnitine levels were not correlated with age, duration of diabetes, fasting blood glucose levels, and glycemic control (HbA1c%) in patients with type 2 diabetes. However, carnitine levels in patient group were correlated with % forced vital capacity (FVC%) (r = 0.35, p = 0.016), % forced expiratory volume in 1 s (FEV1%) (r = 0.318, p= 0.029), FEV1/FVC (r= 0.302, p= 0.039), inspiratory muscle strength (PImax) (r = 0.407, p = 0.023), and PImax% (r = 0.423, p= 0.018). CONCLUSION: This study suggests that low carnitine levels may be associated with lower PImax and PImax% in type 2 diabetes.
Assuntos
Carnitina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Músculos Respiratórios/fisiopatologia , Glicemia/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Estudos Prospectivos , Testes de Função Respiratória , Estatísticas não ParamétricasRESUMO
OBJECTIVE: Glutathione S-transferases (GSTs) comprise a large supergene family and detoxify a variety of endogenous and exogenous electrophilic compounds. Since many GSTs are polymorphic, there has been considerable interest in determining whether particular allelic variants are associated with altered risk for various disorders. RESEARCH DESIGN AND METHODS: In this study the association between the variant GSTM1 0/0 genotype and thyroid carcinoma was investigated. A hospital-based, case-controlled study was carried out. Polymorphisms of GSTM1 0/0 (i.e. the null allele of GSTM1) in samples from 32 cases and 44 controls were detected by polymerase chain reaction (PCR) methodology. The proportions of GSTM1 deleted genotype in cases and controls were 59.4% and 54.5%, respectively. RESULTS: There were significant increments of GSTM 0/0 genotype frequency in a group of patients aged under 40 (p = 0.033, odds ratio (OR) = 4.78, 95% confidence interval (CI) = 1.30-7.13) and in former smokers compared with controls (p = 0.039, OR 2.45, 95% CI 0.216-4.72). CONCLUSION: GSTM1 deleted genotype may be a useful genetic biomarker for thyroid carcinoma susceptibility in young subjects. The absence of this enzyme seems to have a role in the development of thyroid carcinoma; however, the mechanism still needs further study.