An association study between SCFD1 rs10139154 variant and amyotrophic lateral sclerosis in a Chinese cohort
An association study between SCFD1 rs10139154 variant and amyotrophic lateral sclerosis in a Chinese cohort
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SCFD1 rs10139154变异与中国人群肌萎缩侧索硬化症的关联研究
DOI：
10.1080/21678421.2017.1418006
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Shang, Huifang
中科院分区：
文献类型：
--
作者：
Chen, Yongping;Zhou, Qingqing;Shang, Huifang
摘要背景：最近的一项全基因组关联研究（GWAS）表明，Sec 1家族域包含1（SCFD 1）基因与肌萎缩侧索硬化症（ALS）相关。本研究旨在探讨SCFD 1基因rs 10139154单核苷酸多态性（SNP）与ALS的相关性。研究方法：采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析方法对四川大学华西医院神经内科1074例散发性ALS（SALS）患者进行rs 10139154基因分型。此外，还纳入了来自同一地区的927名无关健康对照（HC）。结果如下：调整年龄和性别后，SALS和HC之间以及脊髓发病和延髓发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没有显着差异。值得注意的是，rs 10139154被证明与ALS患者的发病年龄（AAO）相关。一致地，具有“CC”基因型的ALS患者比具有“CG”和“CG + GG”基因型的患者具有更早的平均AAO（分别为p = 0.002和0.001）。结论：我们的研究结果表明，在中国大规模人群中，SCFD 1 rs 10139154与ALS的风险缺乏相关性，但该变异可能会调节ALS的发病年龄。这些发现进一步证明了SCFD 1基因在ALS患者发病机制中的可疑作用。
Abstract Background: 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. Methods: 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. Results: 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). Conclusion: 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.