■叉头盒P3(FOXP3)在自身免疫性疾病的发病机理中起着至关重要的作用。在本研究中,我们对三个单核苷酸多态性进行了基因分型,即,rs2232365,rs3761548和rs3761549,以确定FOXP3多态性与中国北方汉族人群视神经脊髓炎谱系障碍(NMOSD)易感性之间的关系。
■我们使用多重SNaPshot技术对136名NMOSD患者和224名健康受试者的FOXP3基因位点(rs2232365,rs3761548和rs3761549136)的单核苷酸多态性进行了基因分型。等位基因,基因型,和单倍型频率进行了比较。采用qPCR方法分析63例NMOSD患者和35例健康人外周血单个核细胞FOXP3mRNA表达水平。非参数检验用于测试不同组的FOXP3mRNA表达。
■NMOSD组rs222365中G的次要等位基因频率(MAF)明显低于对照组(比值比[OR]=0.57,95%置信区间[95%CI]:0.41-0.79,p=0.001)。利用遗传(共显性,支配,和隐性)模型并进行单倍型分析,在该人群中,rs222365中G的MAF与NMOSD的保护作用相关.此外,单倍型分析表明,单倍型GCT和rs2232365,rs3761548和rs3761549等位基因可预测NMOSD的保护作用(OR=0.63,95%CI=0.41-0.97,p=0.038)。rs2223365(p=0.001)的三种基因型在中度至重度(扩展残疾状态量表(EDSS)≥3分)和轻度(EDSS<3分)组之间没有显着差异。显然,rs2232365患者中AA基因型患者的比例(64.3%)在中重度组中显著高于轻度组(36.4%).然而,rs2232365患者中GG基因型患者的比例(15.2%),轻度组显著高于中重度组(2.9%).NMOSD组FOXP3的mRNA表达明显高于对照组(p=0.001)。然而,急性非治疗组患者的FOXP3mRNA表达低于健康对照组和缓解组患者(分别为p=0.004和0.007).
■FOXP3多态性和单倍型与汉族人群NMOSD易感性相关。FOXP3rs222365的次要等位基因G和单倍型GCT与针对NMOSD的保护相关。GG基因型可能降低NMOSD的严重程度,而AA基因型与中重度NMOSD有关。NMOSD患者的FOXP3mRNA表达高于健康对照组。然而,与健康对照组相比,急性非治疗患者的发病率下降。
UNASSIGNED: Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.
UNASSIGNED: We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.
UNASSIGNED: The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively).
UNASSIGNED: FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.