RESUMO
AIMS: Recently, an association between two polymorphisms (1181G>C and 245T>G) of the osteoprotegerin (OPG) gene and diabetic Charcot neuroarthropathy was suggested on the basis of studies of a limited number of samples derived from subjects from one geographical region (Italy). The aim of this study was to assess the presence of various osteoprotegerin gene polymorphisms in patients with diabetes and Charcot neuroarthropathy compared with subjects with diabetic neuropathy but no Charcot foot and healthy controls from another geographical region (Poland). METHODS: DNA was isolated from 54 patients with Charcot neuroarthropathy, 35 subjects with diabetic neuropathy but no Charcot foot, and 95 healthy controls to evaluate OPG gene polymorphisms and their possible contribution to the development of Charcot neuroarthropathy. RESULTS: Statistically significant differences between the group of subjects with neuropathy but no Charcot neuroarthropathy and the control group were found for 1217C>T, 950T>C and 245T>G polymorphisms, between the group of patients with Charcot neuroarthropathy and the control group for 1181G>C and 950T>C polymorphisms, and between the group of subjects with neuropathy but no Charcot neuroarthropathy and the group of patients with Charcot neuroarthropathy for 1217C>T and 245T>G polymorphisms. CONCLUSION: We suggest that genetic factors, particularly OPG gene polymorphisms, may play a role in the development of diabetic Charcot neuroarthropathy.
Assuntos
Artropatia Neurogênica/genética , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Artropatia Neurogênica/sangue , Artropatia Neurogênica/epidemiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Polônia/epidemiologiaRESUMO
Familial X-chromosome inactivation (XCI) skewing was investigated in a family in which a female mucopolysaccharidosis type II (MPS II) (Hunter syndrome, an X-linked genetic disease) occurred. Among eight related females aged under 60 years from three generations who were tested, four revealed a non-random pattern of XCI. Detailed genetic analysis failed to find mutations in genes that were previously reported as important for the XCI process. Haplotype analysis excluded linkage of non-random XCI with genes localized on the X-chromosome. We propose that analysis of the XCI pattern should be taken into consideration when assessing risk factors for X-linked recessive genetic disorders.
Assuntos
Cromossomos Humanos X/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Iduronato Sulfatase/genética , Mucopolissacaridose II/genética , Inativação do Cromossomo X/genética , Adulto , Idoso , Criança , Feminino , Glicosaminoglicanos/urina , Heterozigoto , Humanos , Lactente , Masculino , Mucopolissacaridose II/urina , Mutação de Sentido Incorreto , LinhagemRESUMO
Lysosomal storage diseases (LSDs) is a group consisting of over 50 disorders caused mostly by dysfunctions of lysosomal proteins and resultant accumulation of particular compounds inside cells and extracellular volumes in affected organisms. Genetic diseases are among the most difficult targets for medical treatment. Nevertheless, understanding of molecular bases of LSDs made it possible to develop novel procedures of treatment, employing molecular medicine. Although various therapeutic approaches have been proposed, and some of them were introduced into clinical practice, none of them was found to be effective in correcting all symptoms in treated patients. Central nervous system and skeleton appear to be the most difficult targets to be improved. Therefore, a proposal appeared that perhaps no single therapeutic procedure may be fully effective in treatment of LSD patients, and only combination of two or more approaches could be a successful therapy. In this review, we present and discuss current stage of various combination therapies for LSDs, based on already available published data.