RESUMO
Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (earliest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regression analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene expression analyses were carried out by RT-qPCR with an independent sample of 35 HD patients from Basque Country Hospitals. We found suggestive association signals between HD eAO and/or mAO and genetic variation within the E2F2, ATF7IP, GRIN2A, GRIN2B, LINC01559, HIP1 and GRIK2 genes. Among them, the most significant was the association between eAO and rs2742976, mapping to the promoter region of E2F2 transcription factor. Furthermore, rs2742976 T allele patient carriers exhibited significantly lower lymphocyte E2F2 gene expression, suggesting a possible implication of E2F2-dependent transcriptional activity in HD pathogenesis. Thus, E2F2 emerges as a new potential HD AO modifier factor.
Assuntos
Genes Modificadores/genética , Doença de Huntington/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idade de Início , Idoso , Alelos , Éxons/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Repetições de Trinucleotídeos/genética , Adulto JovemRESUMO
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No disponible
Assuntos
Humanos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Levodopa/efeitos adversos , Transtornos de Sensação/induzido quimicamente , Transtornos do Sono-Vigília/induzido quimicamente , Dosagem/métodosRESUMO
No disponible
Assuntos
Humanos , Apomorfina/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Domperidona/uso terapêutico , Estimulação Encefálica Profunda , Levodopa/uso terapêuticoRESUMO
Continuous subcutaneous apomorphine infusion (CSAI) is, at present, an alternative option for advanced Parkinson's disease (PD) with motor fluctuations. We studied the evolution of patients with PD and severe motor fluctuations long-term treated with CSAI. We reviewed data from 82 patients with PD (mean age, 67 +/- 11.07; disease duration, 14.39 +/- 5.7 years) and severe motor fluctuations referred to 35 tertiary hospitals in Spain. These patients were long-term treated (for at least 3 months) with CSAI and tolerated the procedure without serious side effects. We compared the baseline data of these 82 patients (before CSAI) with those obtained from the last follow-up visit of each patient. The mean follow-up of CSAI was 19.93 +/- 16.3 months. Mean daily dose of CSAI was 72.00 +/- 21.38 mg run over 14.05 +/- 1.81 hours. We found a statistically significant reduction in off-hours, according to self-scoring diaries (6.64 +/- 3.09 vs. 1.36 +/- 1.42 hours/day, P < 0.0001), total and motor UPDRS scores (P < 0.0001), dyskinesia severity (P < 0.0006), and equivalent dose of antiparkinsonian therapy (1,405 +/- 536.7 vs. 800.1 +/- 472.9 mg of levodopa equivalent units P < 0.0001). CSAI is an effective option for patients with PD and severe fluctuations, poorly controlled by conventional oral drug treatment.
