中国汉族人群CXCR5单核苷酸多态性与NMOSD的相关性

摘要

目的 探讨中国汉族人群中趋化因子受体5(CXCR5)基因单核苷酸多态性(single nucleotide poly-morphism,SNP)与视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)发病的相关性.方法 纳入312例NM OSD患者以及487名年龄、性别相匹配的健康对照人群(HCs).从基因数据库中选出9个CXCR5基因多态性位点(rs11574667、rs523604、rs118182497、rs1623316、rs78146216、rs497916、rs598207、rs676925、rs581063),另一个位点rs10892301来源于系统性红斑狼疮(SLE)的研究.通过对2组等位基因、基因型频率及单倍型分析来探讨CXCR5基因SNP与NMOSD易感性的相关性.结果 NMOSD组与 HCs性别构成及年龄比较差异无统计学意义(均 P> 0.05).等位基因关联分析提示 rs11574667的次等位基因 C 与NMOSD易感性相关(OR=1.33,95% CI:1.01~1.75,P=0.03),经矫正性别及年龄的 Logistic回归分析结果显示,加性、显性及隐形模型中10个SNPs均与NMOSD易感性无关(P>0.05).单倍型分析提示 rs1574667-rs523604-rs118182497的单倍型C-G-G与NMOSD易感性相关(OR=1.50,95% CI:1.00~2.23,P=0.046).结论 中国汉族人群中CXCR5 SNP rs11574667的次等位基因C及 rs1574667-rs523604-rs118182497的单倍型C-G-G与NM OSD易感性相关.有关两者间确切关系尚需进一步研究.%Objective To investigate the genetic association between chemokine receptor-5(CXCR5) polymorphisms and neuromyelitis optica spectrum disorders(NMOSD)in a Han Chinese population.Methods We prospectively consecutively collected 312 patients with NMOSD,as well as 487 age-sex matched healthy controls(HCs).Ten single nucleotide polymorphisms(SNPs)were selected from 1000 Genomes Project (1KGP)database, including rs11574667, rs523604, rs118182497, rs1623316, rs78146216, rs497916, rs598207,rs676925,and rs581063.In addition,a SNPs named rs10892301 was selected from a previous study of another autoimmune disease SLE.The correlation between the CXCR5 SNPs and the susceptibility of NMOSD was investigated by analyzing the alleles,genotype frequencies and haplotypes of these two groups.Results There was no significant difference in gender or age between the patients and the HCs(Both P> 0.05).The allelic association analysis suggested that the minor allele C of rs11574667 was associated with the increased risk of NMOSD(OR=1.33,95% CI:1.01-1.75,P= 0.03).The logistic regression analyses adjusted by gender and age indicated that none of the SNPs was associated with the increased risk of NMOSD under additive, dominant or recessive model(P > 0.05).Haplotype analysis showed that C-G-G of rs1574667-rs523604-rs118182497 was associated with the risk of NMOSD(OR = 1.50,95% CI:1.00-2.23, P = 0.046). Conclusions Our study may suggest that the minor allele C of rs11574667 and haplotype C-G-G of rs1574667-rs523604-rs118182497 were associated with the risk of NMOSD.Further study is needed on the exact relationship between CXCR5 SNPs and NMOSD.