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基因编码一氧化氮合酶和抗氧化酶的变异作为多发性硬化症发展的潜在风险:一项初步研究。

Variation of genes encoding nitric oxide synthases and antioxidant enzymes as potential risks of multiple sclerosis development: a preliminary study.

机构信息

Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236, Lodz, Poland.

Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236, Lodz, Poland.

出版信息

Sci Rep. 2022 Jun 22;12(1):10603. doi: 10.1038/s41598-022-14795-6.

Abstract

Multiple sclerosis (MS) is a neurodegenerative disease characterized by a variable clinical course and diverse pathophysiology, including nitrative and oxidative stresses as well as inflammation. We aimed to detect the potential association between five selected single-nucleotide polymorphisms (SNPs) in genes encoding nitric oxide synthetases as well as antioxidant enzymes and the development of MS in a Polish population. Genomic DNA was isolated from peripheral blood collected from 142 MS patients and 140 controls. Using Taq-Man probes, we genotyped the following SNPs: rs1879417 in NOS1, and rs2297518 in NOS2 as well as rs4880 in SOD2, rs7943316 in CAT, rs713041 in GPX4. In the case of rs2297518, the C/C genotype and C allele SNP were associated with an enhanced occurrence of MS, while the C/T, T/T genotypes, and T allele of the same polymorphism reduced this risk. Moreover, the C/C homozygote and C allele of the rs4880 SNP reduced MS risk, while the T allele increased the risk. In addition, the A/T heterozygote of rs7943316 polymorphism was associated with an increased risk of MS occurrence. We also detected that the C/C genotype and C allele of rs713041 decreased the risk of MS, whereas the T/T genotype and T allele increased this risk. In conclusion, the results of our study suggest some links between polymorphic variability in the nitrative/oxidative stress-related genes and the risk of MS development in the Polish population.

摘要

多发性硬化症(MS)是一种神经退行性疾病,其特征是临床表现多变,病理生理学多样,包括硝化和氧化应激以及炎症。我们旨在检测编码一氧化氮合酶和抗氧化酶的基因中五个选定的单核苷酸多态性(SNP)与波兰人群中 MS 发病之间的潜在关联。从 142 名 MS 患者和 140 名对照者采集的外周血中分离基因组 DNA。使用 Taq-Man 探针,我们对以下 SNP 进行了基因分型:NOS1 中的 rs1879417 和 NOS2 中的 rs2297518 以及 SOD2 中的 rs4880、CAT 中的 rs7943316 和 GPX4 中的 rs713041。对于 rs2297518,C/C 基因型和 C 等位基因 SNP 与 MS 的发生增强相关,而相同多态性的 C/T、T/T 基因型和 T 等位基因降低了这种风险。此外,rs4880 SNP 的 C/C 纯合子和 C 等位基因降低了 MS 的风险,而 T 等位基因增加了风险。此外,rs7943316 多态性的 A/T 杂合子与 MS 发生风险增加相关。我们还发现 rs713041 的 C/C 基因型和 C 等位基因降低了 MS 的风险,而 T/T 基因型和 T 等位基因增加了这种风险。总之,我们的研究结果表明,与硝化/氧化应激相关基因的多态性变异与波兰人群中 MS 发病风险之间存在一些联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/569a/9217808/8991dc55b607/41598_2022_14795_Fig1_HTML.jpg

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