Résumé
Objective: Spinocerebellar ataxia type 2 (SCA2) is one of the most common autosomal dominant ataxias in the world. Several reports revealed that CAG repeats in some polyQ-containing genes may affect the age at onset (AAO) of patients with SCA2, however, little studies were conducted among Chinese patients with SCA2. Thus, the aim of this study is to evaluate the effect of CAG repeats on the AAO of patients with SCA2 in China.Methods:A total of 119 patients with SCA2 were enrolled and were divided into 2 groups according to their major phenotype:17 patients from 9 families with Parkinson ' s syndrome were grouped as the Parkinson ' s disease-SCA2 (PD-SAC2); 91 patients from 66 SCA2 families and 11 sporadic SCA2 patients were grouped as the ataxia-SCA2 (A-SCA2). Blood samples were obtained from the subjects, and the CAG repeat length in ATXN2 and other (CAG)n-containing genes was screened using fluorescent PCR. The Spearman ' s rank correlation between the CAG repeat length in (CAG)n-containing genes and AAO was analyzed. Regression analysis was performed to investigate whether the CAG repeat length could explain the variant of AAO. A t-test was used to compare the difference of CAG repeat length in (CAG)n-containing genes between the PD-SAC2 and A-SCA2 groups. Results:The CAG repeat length in the longer allele of ATXN2 was negatively correlated with AAO of SCA2 (R=?0.251, P<0.05), and the CAG repeat length could explain 41.7％of the variation of AAO. AAO negatively correlated with the CAG repeat length in the shorter allele of ATXN7 (R=?0.251, P=0.006) or in the longer allele of TBP gene (R=?0.197, P=0.034). A tendency of delay in the AAO was also observed in patients with SCA2 carrying the CAG repeat within the ATXN3, CACNA1A, ATXN7, TBP, and RAI1. In addition, we found that the CAG repeat length in ATXN7 and ATXN2 between the A-SCA2 and the PD-SCA2 groups was significantly different (both P<0.05).Conclusion:The CAG repeat in ATXN2 is a major genetic factor for the AAO of patients with SCA2 in China. The CAG repeat length in ATXN3, CACNA1A, ATXN7, TBP, and RAI1 genes might be a potential factor associated with the AAO of SCA2. The CAG repeat in ATXN7 might be a potential factor affecting the Parkinson??s syndrome in SCA2.
Résumé
Objective To investigate the clinical significance of (CAG)n repeats length of androgen receptor (AR) among the patients with metastatic prostate cancer (TxNxM1),and to analyze their relevance to survival.Methods This study retrospectively investigated fifty-three metastatic prostate cancer patients aged 65 years (range 45-87) who were initially treated with endocrine therapy.The length of the (CAG) n repeats of blood samples was determined by both PCR sequencing and fragment analysis.The clinical significance of (CAG)n repeats and its correlation with biochemical progression free survival (bPFS)and overall survival (OS) were investigated.Results The median length of CAG repeats was 21,ranged from 14 to 32.According to the median (CAG)n repeats length,two groups were divided as (CAG)n ≤ 21and(CAG) n≥ 22.The median follow-up was 36 months.Patients with (CAG)n ≤ 21 had significantly shorter OS and bPFS than those with (CAG)n ≥ 22 (P ＜0.05).Shorter CAG repeats remained significant bPFS (HR 2.820,95％CI 1.466-5.427,P=0.002) and OS (HR 5.245,95％CI 1.293-21.27,P=0.020) predictor in multivariate analysis.Conclusions The efficacy of endocrine therapy for metastatic prostate cancer patients maybe influenced by the AR-CAG repeats length,and short (CAG) n repeats predict bad prognosis.