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Fc 受体样 3 多态性(-1901A>G 和-658C>T)与中国人群的视神经脊髓炎易感性显著相关。

Significant Association Between Fc Receptor-Like 3 Polymorphisms (-1901A>G and -658C>T) and Neuromyelitis Optica (NMO) Susceptibility in the Chinese Population.

机构信息

Department of Ophthalmology, the Fourth Affiliated Hospital, China Medical University, 11 Xinhua Road, Heping District, Shenyang, 110005, China.

Department of Medical Image, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.

出版信息

Mol Neurobiol. 2016 Jan;53(1):686-694. doi: 10.1007/s12035-014-9036-7. Epub 2015 Jan 10.

Abstract

Neuromyelitis optica (NMO) is an autoimmune disorder. In pathogenesis, NMO-immunoglobulin G (NMO-IgG) selectively binds to aquaporin-4 (AQP4) and resulted in neuritis, myelitis, and brain lesion. Fc receptor-like 3 (FCRL3) gene encodes a member of the immunoglobulin receptor superfamily, which plays an important part in regulating immune activities. This study aimed at investigating the association between FCRL3 polymorphisms and NMO susceptibility and, hopefully, to contribute to the development of novel methods for diagnosis and treatment of NMO. We selected 150 NMO patients and 300 healthy controls from the Chinese population. Tag single nucleotide polymorphisms (SNPs) were identified with reference to CBI-dbSNP and HapMap databases. DNA were extracted and amplified. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determine the polymorphisms. χ (2), odds ratio (OR), and 95 % confidence interval (95 % CI) were presented to evaluate genotype distribution and association between SNPs and NMO susceptibility. Six out of 15 SNPs were selected according to the filter. No significant altered genotype distribution was observed concerning -11G>C, -166C>T, -219G>C, and -1629C>G polymorphisms. The G allele of -1901A>G variation was demonstrated to be more frequent in patients compared with controls (P < 0.001). The T allele of -658C>T polymorphism was significantly more prevalent in NMO patients than controls (P = 0.009). In summary, the study revealed that the G allele in -1901A>G polymorphism and T allele in -658C>T polymorphism are genetic risk factors for NMO in the Chinese population. Further research is needed to account for different ethnicities and clarify the mechanisms behind, which might contribute to the elucidation of novel diagnosis methods.

摘要

视神经脊髓炎(NMO)是一种自身免疫性疾病。在发病机制中,NMO-免疫球蛋白 G(NMO-IgG)选择性结合水通道蛋白-4(AQP4),导致神经炎、脊髓炎和脑损伤。Fc 受体样 3(FCRL3)基因编码免疫球蛋白受体超家族的一个成员,在调节免疫活性方面发挥着重要作用。本研究旨在探讨 FCRL3 多态性与 NMO 易感性的关系,并希望为 NMO 的诊断和治疗提供新的方法。我们从中国人群中选择了 150 名 NMO 患者和 300 名健康对照者。参考 CBI-dbSNP 和 HapMap 数据库,确定了标签单核苷酸多态性(SNP)。提取和扩增 DNA。基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)用于确定多态性。χ 2 、优势比(OR)和 95%置信区间(95%CI)用于评估 SNP 与 NMO 易感性之间的基因型分布和关联。根据筛选标准,选择了 15 个 SNP 中的 6 个。-11G>C、-166C>T、-219G>C 和-1629C>G 多态性的基因型分布无明显改变。与对照组相比,-1901A>G 变异的 G 等位基因在患者中更为常见(P<0.001)。-658C>T 多态性的 T 等位基因在 NMO 患者中明显更为常见(P=0.009)。总之,该研究表明,-1901A>G 多态性中的 G 等位基因和-658C>T 多态性中的 T 等位基因是中国人群 NMO 的遗传危险因素。需要进一步研究以考虑不同的种族,并阐明背后的机制,这可能有助于阐明新的诊断方法。

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