RESUMO
Mutations in the hepatocyte nuclear factor-1beta (HNF-1beta) gene have been shown to be a cause of maturity-onset diabetes of the young (MODY). We studied the contribution of the HNF-1beta gene to susceptibility to common forms of Type 2 diabetes in the genetically homogeneous Japanese population, by investigating the allelic association of Type 2 diabetes with two markers in the HNF-1beta region. The frequency of a nonsense mutation, R177X, which was previously reported in a Japanese family, was also studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method using a mismatch primer. A total of 200 subjects were studied. There was no significant difference in allele frequencies of either of the two polymorphisms studied between patients with Type 2 diabetes and control subjects, or between subgroups of patients subdivided by the presence of mild or severe diabetic nephropathy. None of the subjects studied had R177X mutation, giving a frequency of less than 1.1% in common forms of Type 2 diabetes in Japan. These results suggest that mutations in the HNF-1beta gene derived from a limited number of founders are not a major cause of common forms of Type 2 diabetes, even in the genetically homogeneous Japanese population.
Assuntos
Proteínas de Ligação a DNA/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Fatores de Transcrição/genética , Adulto , Idoso , Alelos , Nefropatias Diabéticas/genética , Feminino , Frequência do Gene , Fator 1-beta Nuclear de Hepatócito , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), and patched (Ptc; a receptor for Ihh) were immunolocalized in tissue undergoing endochondral ossification in the human. PTHrP, Ihh, and Ptc were immunolocalized in prehypertrophic and hypertrophic chondrocytes in mature cartilage matrix. PTHrP and Ptc were immunostained in proliferating chondrocytes and perichondrial cells, whereas Ihh was not. PTHrP, Ihh, and Ptc showed positive immunostaining in osteoblasts in the bone-forming area. In the bone resorption site, PTHrP was immunolocalized in osteoclasts, whereas Ihh and Ptc were not. The present findings indicated that PTHrP, Ihh, and Ptc were associated with the process of endochondral ossification, and suggested the possible involvement of Ihh and PTHrP signaling in the regulation of proliferation and hypertrophy of chondrocytes in human chondrogenesis.
Assuntos
Osso e Ossos/metabolismo , Osteogênese , Proteínas/análise , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/fisiopatologia , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Divisão Celular/genética , Condrócitos/metabolismo , Colágeno Tipo I/genética , Proteínas Hedgehog , Humanos , Hipertrofia , Imuno-Histoquímica , Hibridização In Situ , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Osteoblastos/metabolismo , Osteocondroma/genética , Osteocondroma/metabolismo , Osteocondroma/fisiopatologia , Osteoclastos/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo , Receptores Patched , Polidactilia/genética , Polidactilia/metabolismo , Polidactilia/fisiopatologia , Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Superfície Celular , Transativadores/análise , Transativadores/genéticaRESUMO
Autoantibodies against IA-2 have been detected in up to 86% of newly diagnosed patients with type 1 diabetes and appear to identify a subgroup of prediabetic subjects who rapidly progress to type 1 diabetes. We examined the association of IA-2 gene polymorphism with type 1 diabetes in Japanese subjects. A total of 276 Japanese subjects were studied for disease association and, in addition, another 53 patients were studied for association with the autoantibody status to IA-2. A microsatellite marker D2S1753E, located in the intron of the IA-2 gene, was used as a genetic marker in this study. In Japanese, two alleles (161mu and 165mu) were more frequent, and the 163mu allele was less frequent than in Caucasians (p = 0.0001). There was no significant difference in frequencies of alleles between diabetic patients and control subjects. The frequency of IA-2 gene polymorphism was not significantly different between patients stratified by age-at-onset, or between patients with and without susceptible HLA, DRB1*0405, DRB1*0802 and DRB1*0901. There was no significant difference in allele frequency of the IA-2 gene polymorphism between patients with and without autoantibody to IA-2. In conclusion, IA-2 gene polymorphism is not associated with either susceptibility to, or heterogeneity in type 1 diabetes in Japanese subjects.
Assuntos
Povo Asiático/genética , Autoantígenos/genética , Diabetes Mellitus Tipo 1/genética , Ilhotas Pancreáticas , Proteínas de Membrana/genética , Polimorfismo Genético , Proteínas Tirosina Fosfatases/genética , Alelos , Autoanticorpos/imunologia , Autoantígenos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Frequência do Gene , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Humanos , Japão , Proteínas de Membrana/imunologia , Proteína Tirosina Fosfatase não Receptora Tipo 1 , Proteínas Tirosina Fosfatases/imunologia , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a ReceptoresRESUMO
A 70-year-old man, with mild-type myotonic dystrophy (MyD) diagnosed by molecular genetic analysis when he was 68 years old, complained of worsening intermittent claudication during the past 2 years. Doppler examination revealed severe stenosis and obstruction in his leg arteries, which we diagnosed as arteriosclerosis obliterans (ASO). We then found him to be suffering from dementia, which was confirmed by dementia scale tests (Mini Mental State, 20/30; Hasegawas' Dementia Scale-Revision, 15/30). Even in mild-type MyD, as MyD is one of the progeria syndromes, the abnormal genes of MyD may accelerate the aging processes.