散发性肌萎缩侧索硬化单核苷酸多态位点质谱分型及疾病易患性关联分析

Single nucleotide polymorphism associated with Chinese sporadic amyotrophic lateral sclerosis patient

目的肌萎缩侧索硬化（amyotrophic lateral sclerosis，AGS）是由上、下运动神经元进行性丢失引起的一种致死性疾病，散发性ALS（SAGS）近90％，目前认为是一种复杂性疾病。已有数个ALS全基因组关联分析研究先后报道了若干与增加ALS发病风险相关的单核苷酸多态（SNP）位点，但亚洲人资料较少。我们将筛查与增加中国人SAGS致病风险相关的SNP。方法提取样本外周血基因组DNA，进行病例组和对照组年龄、性别匹配，质谱法分型筛选出的SNP位点并进行关联分析。结果完成86例SAGS患者与94名对照者rs6700125、rs10260404、rs1942239、rs2279812、rs2405657、rs558889、rs6922711、rs9351470等8个SNP位点的基因分型，统计分析后两组差异无统计学意义。合并Cronin等研究数据后rs1942239（邻近基因GALNT1）的P值减小（由1．48×10^-4减少为9．07×10^-5），关联性增强。rs558889的病例组基因频率偏离Hardy—Weinberg平衡，可能存在关联。结论rs1942239和rs558889两个SNP可能与增加中国人SAGS致病风险相关，与rs1942239邻近的GALNT1基因和rs558889附近的ANK1基因值得进一步研究。

Objective Amyotrophic lateral sclerosis （ALS） is a progressive paralytic disorder resulting from the degeneration of upper and lower motor neurons. Sporadic ALS （SALS） accounts for majority of patients. ALS is a kind of complex disorder. There were several single nucleotide polymorphism （SNP） reported to be associated with SALS in recently published genome-wide association （GWA） study, but there are few data from Asia ALS population and no report focus on SNP which may associated with SALS of Chinese origin. Our study is to screen and add the SNPs related to the risks of SALS in Chinese. Methods Eighty-six individuals with SALS and 94 matched controls were recruited for our study and genomic DNA from blood samples was extracted. Genotypes were determined by a matrix assisted laser desorption/ ionization time of flight mass spectrometry based approach followed by association analysis. Results Individual genotype data for 8 SNPs, rs6700125, rs10260404, rs1942239, rs2279812, rs2405657, rs558889, rs6922711 and rs9351470 in Chinese population showed no significant association with sporadic ALS. Combining genotype data from published GWA, rs1942239 gained in strength of allelie association（ P value decreased to 9.07×10^-5 from 1.48×10^-4 ） , and rs558889 deviated Hardy-Weinberg equilibrium at ALS case group which may be associated with susceptibility. Conclusions SNP rs1942239 and rs558889 may contribute to susceptibility of sporadic ALS in Chinese patient. The larger sample studies are warranted to confirm the association.