Department of Neurology, Xiangya Hospital, Central south university, xiangya road, Changsha, China.
BMC Neurol. 2013 Apr 26;13:38. doi: 10.1186/1471-2377-13-38.
Eukaryotic translation initiation factor 4-gamma 1 (EIF4G1) gene mutations have recently been reported in autosomal dominant, late-onset Parkinson's disease (LOPD). We carried out genetic analysis to determine the prevalence of EIF4G1 variants in an ethnic Chinese population and to better understand the association between EIF4G1 and PD.
We conducted a comprehensive genetic analysis of EIF4G1 in a cohort of 29 probands of autosomal dominant, LOPD families. Polymerase chain reaction (PCR) analysis and sequencing was carried out of the entire EIF4G1 exonic regions and exon-intron boundaries. Specific mutation and exonic variants were chosen for further sequencing in a case-control study including 503 sporadic PD and 508 healthy controls. Statistical significance was analyzed by the Chi-square test.
Our analysis revealed three exonic variants (rs2230571, rs13319149 and rs2178403) and eight intronic variants across the entire EIF4G1 gene. No reported mutations were detected in EIF4G1 exonic regions. The synonymous coding variant rs2230571 in exon 27 and the eight intronic variants were not used for further sequencing, but the specific mutation c.3614G > A (p.R1205H) and the two nonsynonymous variants (rs13319149 and rs2178403) were chosen for further analysis in a case-control study. None of the 503 sporadic PD or 508 healthy controls carried p.R1205H, and there was no statistical significance in rs2178403 genotype or allele frequencies in EIF4G1 between the PD cases and the healthy controls (p = 0.184 and p = 0.774, respectively; Chi-square test). The rs13319149 genotype in all PD cases and healthy controls was GG.
Our data indicate that in an ethnic Chinese population, the pathogenic mutation p.R1205H in EIF4G1 is not common and that EIF4G1 exonic variants rs2178403 and rs13319149 are not associated with PD. EIF4G1 does not appear to be a frequent cause of PD in this ethnic Chinese population.
真核翻译起始因子 4-γ 1（EIF4G1）基因突变最近被报道与常染色体显性遗传、晚发性帕金森病（LOPD）有关。我们进行了基因分析，以确定 EIF4G1 变体在中国人群中的流行率，并更好地了解 EIF4G1 与 PD 之间的关联。
我们对 29 个常染色体显性遗传、LOPD 家族的先证者进行了 EIF4G1 的全面基因分析。采用聚合酶链反应（PCR）分析和测序方法对整个 EIF4G1 外显子区域和外显子-内含子边界进行了分析。在包括 503 例散发性 PD 和 508 例健康对照的病例对照研究中，选择特定的突变和外显子变体进行进一步测序。采用卡方检验分析统计学意义。
我们的分析显示，在整个 EIF4G1 基因中存在三个外显子变体（rs2230571、rs13319149 和 rs2178403）和八个内含子变体。在外显子区域未发现报道的突变。外显子 27 中的同义编码变体 rs2230571 和八个内含子变体未用于进一步测序，但选择了特定的突变 c.3614G>A（p.R1205H）和两个非同义变体（rs13319149 和 rs2178403）进行进一步的病例对照研究。在 503 例散发性 PD 或 508 例健康对照中，没有携带 p.R1205H，并且在 PD 病例和健康对照之间，EIF4G1 中的 rs2178403 基因型或等位基因频率没有统计学意义（p=0.184 和 p=0.774，分别；卡方检验）。所有 PD 病例和健康对照的 rs13319149 基因型均为 GG。
我们的数据表明，在中国人群中，EIF4G1 中的致病突变 p.R1205H 并不常见，EIF4G1 外显子变体 rs2178403 和 rs13319149 与 PD 无关。EIF4G1 似乎不是该中国人群中 PD 的常见病因。
