RESUMO
BACKGROUND AND PURPOSE: Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed. METHODS: To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire. RESULTS: Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P = 0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently associated with positive PRRT2 mutation. CONCLUSIONS: PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.
Assuntos
Coreia/genética , Predisposição Genética para Doença/genética , Proteínas de Membrana/genética , Mutação/genética , Proteínas do Tecido Nervoso/genética , Idade de Início , Povo Asiático , Criança , Coreia/diagnóstico , Distonia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Análise de Regressão , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.
