PDF(Pubmed)
Abstract：
In this study, the potential role and interaction of the APOε and KLOTHO genes on the penetrance of fragile X-associated tremor/ataxia syndrome (FXTAS) and on the IQ trajectory were investigated. FXTAS was diagnosed based on molecular, clinical and radiological criteria. Males with the premutation (PM) over 50 years, 165 with and 34 without an FXTAS diagnosis, were included in this study and were compared based on their APO (ε2-ε3-ε4) and KLOTHO variant (KL-VS) genotypes. The effect of APOε4 on FXTAS stage and on diagnosis did not differ significantly by KL-VS genotype with interaction effect p = 0.662 and p = 0.91, respectively. In the FXTAS individuals with an APOε2 allele, a marginal significance was observed towards a larger decline in verbal IQ (VIQ) in individuals with an APOε4 allele compared to those without an APOε4 allele (p = 0.071). In conclusion, our findings suggest that the APOε4 and KL-VS genotypes alone or through their interaction effect do not appear to predispose to either FXTAS diagnosis or stage in male carriers of the PM allele. A further study is needed to establish the trend of IQ decline in the FXTAS individuals who carry APOε4 with APOε2 compared to those without APOε4.
摘要：
在这项研究中,研究了APOε和KLOTHO基因对脆性X相关震颤/共济失调综合征(FXTAS)外显率和智商轨迹的潜在作用和相互作用。FXTAS是根据分子诊断的，临床和放射学标准。具有超过50年的前突变（PM）的雄性，165和34没有FXTAS诊断，纳入本研究，并根据其APO（ε2-ε3-ε4）和KLOTHO变体（KL-VS）基因型进行比较。APOε4对FXTAS分期和诊断的影响在KL-VS基因型之间没有显着差异，相互作用效应分别为p=0.662和p=0.91。在具有APOε2等位基因的FXTAS个体中，与没有APOε4等位基因的个体相比，具有APOε4等位基因的个体的言语智商（VIQ）下降幅度更大（p=0.071）。总之,我们的发现表明，APOε4和KL-VS基因型单独或通过它们的相互作用效应似乎不容易在PM等位基因的男性携带者中进行FXTAS诊断或分期。需要进一步的研究来确定与无APOε4相比，携带APOε2的FXTAS个体的智商下降趋势。
