Ogasawara Mikihide, Meguro Akira, Sakai Tsutomu, Mizuki Nobuhisa, Takahashi Toshiyuki, Fujihara Kazuo, Tsuneoka Hiroshi, Shikishima Keigo
Department of Ophthalmology, Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo, 105-8461, Japan.
Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Japan.
Jpn J Ophthalmol. 2016 May;60(3):198-205. doi: 10.1007/s10384-016-0441-5. Epub 2016 Mar 25.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disorder that generally affects the optic nerve and spinal cord. The etiology of this disease is still uncertain, but autoantibodies to aquaporin-4 (AQP4) are specific and pathogenic for NMO. Recent studies show that AQP4 gene variants are associated with NMO. In this study, we assessed the contribution of AQP4 genetic variants to susceptibility to anti-AQP4 antibody (AQP4-Ab)-positive NMO in a Japanese population.
The subjects were 16 patients with AQP4-Ab-positive NMO (13 sporadic cases, and 3 familial cases from 2 families) and 255 healthy controls. All coding exons of AQP4 were sequenced and five tag single-nucleotide polymorphisms (SNPs) in AQP4 were genotyped. We also performed an imputation analysis to evaluate the potential association of un-genotyped SNPs in AQP4.
Known or novel mutations were not detected in any coding exon regions. The T allele frequency of polymorphism (-810 bp (C/T): rs2075575) of the promoter region in patients with AQP4-Ab-positive NMO was significantly higher than that in controls (50.0 vs 25.7 %, P = 0.0036, Pc = 0.018 odds ratio = 2.89). No other tag or imputed SNPs were significant.
These findings suggest that the T allele of rs2075575 is a risk for AQP4-Ab-positive NMO. However, the results are the opposite of a previous study in the southern Han Chinese population, and therefore further genetic studies are needed to determine the possible contribution of the AQP4 region to development of NMO.
视神经脊髓炎（NMO）是一种炎症性脱髓鞘疾病，通常累及视神经和脊髓。该病的病因仍不确定，但水通道蛋白4（AQP4）自身抗体对NMO具有特异性且具有致病性。最近的研究表明，AQP4基因变异与NMO有关。在本研究中，我们评估了AQP4基因变异对日本人群中抗AQP4抗体（AQP4-Ab）阳性NMO易感性的影响。
研究对象为16例AQP4-Ab阳性NMO患者（13例散发病例和来自2个家庭的3例家族病例）和255名健康对照。对AQP4的所有编码外显子进行测序，并对AQP4中的5个标签单核苷酸多态性（SNP）进行基因分型。我们还进行了推断分析，以评估AQP4中未基因分型的SNP的潜在关联。
在任何编码外显子区域均未检测到已知或新的突变。AQP4-Ab阳性NMO患者启动子区域多态性（-810 bp（C/T）：rs2075575）的T等位基因频率显著高于对照组（50.0%对25.7%，P = 0.0036，Pc = 0.018，优势比 = 2.89）。没有其他标签或推断的SNP具有显著性。
这些发现表明，rs2075575的T等位基因是AQP4-Ab阳性NMO的一个风险因素。然而，结果与先前对中国南方汉族人群的研究相反，因此需要进一步的遗传学研究来确定AQP4区域对NMO发病可能的影响。
