Qiu Wei, Chang Yanyu, Li Rui, Long Youming, Huang Jianhua, Mai Weihua, Sun Xiaobo, Lu Zhengqi, Hu Xueqiang
Department of Neurology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Email:
Zhonghua Yi Xue Za Zhi. 2015 Feb 17;95(7):501-6.
To explore the correlation between aquaporin-4 (AQP4) gene single nucleotide polymorphism (SNP) and clinical phenotypes of neuromyelitis optica (NMO) and its underlying mechanism.
Eight SNPs in AQP4 gene regulatory region were selected and genotyped for 208 anti-AQP4 autoantibodies (NMO-IgG) seropositive cases during January 2010 to January 2014 and 204 healthy subjects. Then the correlation was further analysed between genotypes and NMO phenotypes. And the effect of microRNA (miRNA) on the expression of AQP4 gene was examined by dual-luciferase reporter technique.
The A/T genotype of rs1058424 (50.61% vs 70.45%, OR = 0.430, 95% CI 0.210-0.880) and C/T (50.00% vs 68.18%, OR = 0.467, 95%CI 0.231-0.994) genotype of rs3763043 in 3'-UTR were correlated with longitudinal extensive transverse myelitis; the A/T genotype of rs1058424 (46.72% vs 66.28%, OR = 0.525, 95% CI 0.276-0.999) and A/C genotype of rs335929 (45.08% vs 58.14%, OR = 0.527, 95% CI 0.281-0.987) in 3'-UTR as well as C/T genotype of rs151244 (50.82% vs 69.77%, OR = 0.450, 95% CI 0.230-0.881) in promoter 0 region were correlated with optic neuritis. The polymorphism of rs6508459 in 3'-UTR and rs3763040 in intron region were correlated with concurrent systemic autoimmune diseases (P = 0.012 and 0.023 respectively).miRNA 323-3p could regulate AQP4 gene expression.However, variation in SNP rs1058424 failed to affect this regulation.
SNP in 3'-UTR of AQP4 gene may be associated with NMO phenotypes.miRNA 323-3p may participate in the pathogenesis of NMO by binding to certain SNP sites in 3'-UTR of AQP4 gene and regulating its expression.
探讨水通道蛋白4（AQP4）基因单核苷酸多态性（SNP）与视神经脊髓炎（NMO）临床表型的相关性及其潜在机制。
选取AQP4基因调控区的8个SNP，对2010年1月至2014年1月期间的208例抗AQP4自身抗体（NMO-IgG）血清阳性患者及204例健康对照者进行基因分型。进一步分析基因型与NMO表型之间的相关性。采用双荧光素酶报告技术检测微小RNA（miRNA）对AQP4基因表达的影响。
3'-UTR区rs1058424的A/T基因型（50.61%对70.45%，OR = 0.430，95%CI 0.210 - 0.880）和rs3763043的C/T基因型（50.00%对68.18%，OR = 0.467，95%CI 0.231 - 0.994）与纵向广泛横贯性脊髓炎相关；3'-UTR区rs1058424的A/T基因型（46.72%对66.28%，OR = 0.525，95%CI 0.276 - 0.999）、rs335929的A/C基因型（45.08%对58.14%，OR = 0.527，95%CI 0.281 - 0.987）以及启动子0区rs151244的C/T基因型（50.82%对69.77%，OR = 0.450，95%CI 0.230 - 0.881）与视神经炎相关。3'-UTR区rs6508459和内含子区rs3763040的多态性与并发的系统性自身免疫疾病相关（P分别为0.012和0.023）。miRNA 323 - 3p可调节AQP4基因表达。然而，SNP rs1058424的变异未能影响这种调节作用。
AQP4基因3'-UTR区的SNP可能与NMO表型相关。miRNA 323 - 3p可能通过与AQP4基因3'-UTR区的某些SNP位点结合并调节其表达而参与NMO的发病机制。
