Chen Yongping, Zhou Qingqing, Gu Xiaojing, Wei Qianqian, Cao Bei, Liu Hui, Hou Yanbing, Shang Huifang
a Department of Neurology , West China Hospital, Sichuan University , Chengdu , Sichuan , China.
Amyotroph Lateral Scler Frontotemporal Degener. 2018 Aug;19(5-6):413-418. doi: 10.1080/21678421.2017.1418006. Epub 2017 Dec 20.
A recent genome-wide association study (GWAS) demonstrated that the Sec1 family domain containing 1 (SCFD1) gene is associated with amyotrophic lateral sclerosis (ALS). The objective of our study was to investigate the association between the single nucleotide polymorphism (SNP) rs10139154 in the SCFD1 gene and ALS in a Chinese cohort.
A cohort of 1074 sporadic ALS (SALS) patients from the Department of Neurology at the West China Hospital of Sichuan University were genotyped for rs10139154 using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. In addition, 927 unrelated healthy controls (HCs) from the same region were included.
After adjusting for age and sex, no significant differences in the genotype distributions and allele frequencies in the allelic, additive, dominant or recessive genetic models were found between SALS and HCs and between patients with spinal onset and bulbar onset. Remarkably, rs10139154 was shown to be associated with the age at onset (AAO) of ALS patients. Consistently, ALS patients with the "CC" genotype have an earlier mean AAO than that of patients with a "CG" and "CG + GG" genotype (p = 0.002 and 0.001, respectively).
Our results suggest that there is a lack of association of SCFD1 rs10139154 with the risk for ALS in a large Chinese population, but this variant may modulate the age of onset of ALS. These findings add further evidence to the suspected implication of the SCFD1 gene in the pathogenesis of disease in our ALS population.
最近一项全基因组关联研究（GWAS）表明，含Sec1家族结构域1（SCFD1）基因与肌萎缩侧索硬化症（ALS）相关。我们研究的目的是在中国人群中调查SCFD1基因单核苷酸多态性（SNP）rs10139154与ALS之间的关联。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析，对四川大学华西医院神经内科的1074例散发性ALS（SALS）患者进行rs10139154基因分型。此外，纳入了来自同一地区的927名无血缘关系的健康对照（HC）。
在调整年龄和性别后，SALS患者与HC之间以及脊髓起病和延髓起病患者之间，在等位基因、加性、显性或隐性遗传模型中的基因型分布和等位基因频率均无显著差异。值得注意的是，rs10139154与ALS患者的发病年龄（AAO）相关。一致地，“CC”基因型的ALS患者平均AAO比“CG”和“CG + GG”基因型的患者更早（分别为p = 0.002和0.001）。
我们的结果表明，在一大群中国人群中，SCFD1 rs10139154与ALS风险缺乏关联，但该变体可能调节ALS的发病年龄。这些发现为SCFD1基因在我们ALS人群疾病发病机制中的潜在作用提供了进一步的证据。
