RESUMO
BACKGROUND: Osteoporosis is a highly heritable trait. Among the genes associated with bone mineral density (BMD), the low-density lipoprotein receptor-related protein 5 gene (LRP5) has been consistently identified in Caucasians. However LRP5 contribution to osteoporosis in populations of other ethnicities remains poorly known. METHODS: To determine whether LRP5 polymorphisms Ala1330Val and Val667Met are associated with BMD in North Africans, these genotypes were analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 ± 7 .7 years, of which 59.1% have low bone mass (T-score<-1 at spine or hip). RESULTS: In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC genotypes tended to be more frequent in women with osteopenia and osteoporosis than in women with normal BMD (p=0.066). Adjusting for body size and other potential confounders, LRP5 genotypes were no longer significantly associated with aBMD at any site. CONCLUSIONS: The less common Val667Met polymorphism showed no association with osteoporosis. The Ala1330Val polymorphism is weakly associated with lower lumbar spine bone density and osteopenia/osteoporosis in postmenopausal Tunisian women. These observations expand our knowledge about the contribution of LRP5 genetic variation to osteoporosis risk in populations of diverse ethnic origin.
Assuntos
Densidade Óssea/genética , Estudos de Associação Genética , Genótipo , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/genética , Idoso , Feminino , Estudos de Associação Genética/métodos , Humanos , Vértebras Lombares/patologia , Vértebras Lombares/fisiologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Tunísia/epidemiologiaAssuntos
Transtornos Herdados da Coagulação Sanguínea/genética , Mutação , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/genética , Pré-Escolar , Fator V/metabolismo , Deficiência do Fator V/genética , Fator VIII/metabolismo , Humanos , Masculino , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Conformação ProteicaRESUMO
Inherited factor VII (FVII) deficiency is a rare disorder characterized by a bleeding phenotype varying from mild to severe. To date, more than 200 mutations have been described along the F7 gene encoding for FVII. The aim of this study was the identification of genetic defects underlying FVII deficiency in 10 patients belonging to eight unrelated families of the North provinces from Tunisia. Mutation detection was performed by sequencing the whole F7 gene coding region, exon-intron boundaries and about 400 bp of the promoter region. We identified 5 mutations in five unrelated families; the novel p.F328Y mutation and the reported mutations: p.R304Q, p.M298I, IVS1aG > A and p.G-39G. For the remaining 5 patients we didn't identified any mutations using PCR/Sequencing protocol. In conclusion, this study represents the first comprehensive molecular series of FVII deficiency affected patients in Tunisia from the North. We will try in the future to continue the molecular study for Tunisian patients from Center and South provinces in order to have a complete idea about the FVII deficiency mutational profile in our country. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1288044089753085.
Assuntos
Coagulação Sanguínea/genética , Deficiência do Fator VII/genética , Fator VII/genética , Mutação , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Fatores de Coagulação Sanguínea/uso terapêutico , Coagulantes/uso terapêutico , Contusões/sangue , Contusões/genética , Análise Mutacional de DNA , Epistaxe/sangue , Epistaxe/genética , Éxons , Deficiência do Fator VII/sangue , Deficiência do Fator VII/tratamento farmacológico , Deficiência do Fator VII/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Íntrons , Masculino , Menorragia/sangue , Menorragia/genética , Metrorragia/sangue , Metrorragia/genética , Pessoa de Meia-Idade , Fenótipo , Regiões Promotoras Genéticas , Tunísia/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: We investigated two genetic markers in pro inflammatory molecules : TNFalpha -308G/A and IL6 -174G/C in order to assess their effect on type 2 diabetes (T2D) and obesity in the Tunisian population. DESIGN AND METHODS: The study sample includes 228 patients with T2D and 300 healthy controls. Genotyping of IL6 -174G/C (rs1800795) was performed using Automated Dye Terminator Sequencing and of TNFalpha -308G/A (rs1800629) using the LightTyper technology. RESULTS: SNPs IL6 -174G/C and TNFalpha -308G/A are associated neither with T2D (p=0.89, p=0.34 respectively) nor with risk for overweight (p=0.86, p=0.12 respectively) in Tunisian population. Bonferroni correction showed that the founded association of IL6 -174G/C SNP with T2D susceptibility restricted to overweight patients (p(nominal)=0.03, p(corrected)=0.0033) is likely to be a random result. CONCLUSION: SNPs IL6 -174G/C and TNFalpha -308G/A are not major contributors to T2D or obesity risk in our Tunisian population.