Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Am J Hum Genet ; 75(6): 1032-45, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15514891

RESUMO

Osteoporosis has a strong genetic component, but the genes involved are poorly defined. We studied whether the sclerosteosis/van Buchem disease gene (SOST) is an osteoporosis-risk gene by examining its association with bone-mineral density (BMD). Mutations in SOST result in sclerosteosis, and alterations in the SOST gene expression may be causal in the closely related van Buchem disease. We used a set of eight polymorphisms from the SOST gene region to genotype 1,939 elderly men and women from a large population-based prospective-cohort study of Dutch whites. A 3-bp insertion (f=0.38) in the presumed SOST promoter region (SRP3) was associated with decreased BMD in women at the femoral neck (FN) (P=.05) and lumbar spine (LS) (P=.01), with evidence of an allele-dose effect in the oldest age group (P=.006). Similarly, a G variant (f=0.40) in the van Buchem deletion region (SRP9) was associated with increased BMD in men at the FN (P=.007) and LS (P=.02). In both cases, differences between extreme genotypes reached 0.2 SD. We observed no genotype effects on fracture risk, for the 234 osteoporotic fractures validated during 8.2 years of follow-up and for the 146 vertebral prevalent fractures analyzed. We did not find association between any of several frequent haplotypes across the SOST gene region and BMD. We did find evidence of additive effects of SRP3 with the COLIA1 Sp1 polymorphism but not with haplotypes of 3' polymorphisms in the vitamin-D receptor gene. The SOST-COLIA1 additive effect increased with age and reached 0.5 SD difference in BMD at LS in the oldest age group (P=.02). The molecular mechanism whereby these moderate SOST genotype effects are mediated remains to be elucidated, but it is likely to involve differences in regulation of SOST gene expression.


Assuntos
Densidade Óssea/genética , Proteínas Morfogenéticas Ósseas/genética , Marcadores Genéticos/genética , Osteoporose/genética , Polimorfismo Genético , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Análise de Variância , Proteínas Morfogenéticas Ósseas/metabolismo , Estudos de Coortes , Primers do DNA , Feminino , Frequência do Gene , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Países Baixos , Razão de Chances , Regiões Promotoras Genéticas/genética , Análise de Regressão , Análise de Sequência de DNA , Traumatismos da Coluna Vertebral/genética , Traumatismos da Coluna Vertebral/patologia , População Branca
2.
Am J Med Genet ; 110(2): 144-52, 2002 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-12116252

RESUMO

Van Buchem disease is an autosomal recessive sclerosing bone dysplasia characterized by skeletal hyperostosis, overgrowth of the mandible, and a liability to entrapment of the seventh and eighth cranial nerves. The genetic determinant maps to chromosome 17q12-q21. We refined the critical interval to the < 1-Mb region between D17S2250 and D17S2253 in 15 affected individuals, all of whom shared a common disease haplotype. Furthermore, we report here the identification of a 52-kb deletion located within the interval and encompassing D17S1789 that is 100% concordant with the disorder. Although the deletion itself does not appear to disrupt the coding region of any known or novel gene(s), the closest flanking genes are MEOX1 on the proximal side, and SOST on the distal side of the deletion. MEOX1 is known to be important for the development of the axial skeleton, whereas the SOST gene is the determinant of sclerosteosis, a disorder that shares many features with van Buchem disease, thus raising the possibility that van Buchem disease results from dysregulation of the expression of one or both of these genes.


Assuntos
Proteínas Morfogenéticas Ósseas , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Marcadores Genéticos , Osteocondrodisplasias/genética , Proteínas Adaptadoras de Transdução de Sinal , África , Sequência de Bases , DNA Intergênico/genética , Feminino , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Países Baixos , Osteocondrodisplasias/patologia , Osteosclerose/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética
4.
J Org Chem ; 61(8): 2709-2712, 1996 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-11667102

RESUMO

Two new alkaloids, polycarpine (1) and N,N-didesmethylgrossularine-1 (4), have been isolated from extracts of the ascidian Polycarpa aurata collected in Chuuk, Federated States of Micronesia. Three degradation products of 1 were also isolated. The structures of 1, 2, and 4 were determined by X-ray crystallography. The dimeric disulfide 1 inhibited the enzyme inosine monophosphate dehydrogenase, but the inhibition could be reversed by addition of excess dithiothreitol suggesting that 1 reacts with sulfhydryl groups on the enzyme.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...