Bunjevacki Vera, Maksimovic Nela, Jekic Biljana, Milic Vera, Lukovic Ljiljana, Novakovic Ivana, Damjanov Nemanja, Radunovic Goran, Damnjanovic Tatjana
Faculty of Medicine, Institute of Human Genetics, University of Belgrade, 26 Visegradska Str., Belgrade, 11000, Serbia.
Faculty of Medicine, Institute of Rheumatology, University of Belgrade, Resavska 69 Str., Belgrade, Serbia.
Rheumatol Int. 2016 Apr;36(4):597-602. doi: 10.1007/s00296-015-3401-3. Epub 2015 Nov 26.
Nitric oxide (NO) is a mediator in autoimmune responses and thus involved in the pathogenesis of a variety of rheumatic diseases. Genetic factors that influence the expression of the enzyme endothelial nitric oxide synthase (eNOS) that catalyzes NO synthesis are important for the control of NO level and consequently its activity. We have analyzed three functionally relevant polymorphisms of eNOS gene: T-786C, G894T and VNTR (4a/b), to investigate whether they are predisposing factors in pathogenesis of RA in Serbian population and to evaluate their role in clinical manifestations of RA. We performed genotyping of 196 patients with RA and the control group of 132 healthy individuals from Serbian population, using PCR and polymerase chain reaction-restriction fragment length polymorphism methods. Disease activity was prospectively assessed using number of tender joints, number of swollen joints and 28-joints disease activity score (DAS28). There were no differences between the patients and control groups in the genotypes and alleles frequencies of the three analyzed SNPs. Our results showed statistically significant differences in all three analyzed parameters of disease severity between 786TT/786CT and 786CC genotypes and between 894GG/894GT and 894TT genotypes. In the case of 4a/b polymorphism, carriers of minor allele had significantly lower DAS28 values. In conclusion, our results do not support the implication of analyzed eNOS gene polymorphisms in susceptibility to RA but associate them with the disease activity and give assumption that minor alleles are indicators of better clinical course.
一氧化氮（NO）是自身免疫反应中的一种介质，因此参与多种风湿性疾病的发病机制。影响催化NO合成的内皮型一氧化氮合酶（eNOS）表达的遗传因素对于控制NO水平及其活性至关重要。我们分析了eNOS基因的三个功能相关多态性：T-786C、G894T和VNTR（4a/b），以研究它们是否是塞尔维亚人群类风湿关节炎（RA）发病机制中的易感因素，并评估它们在RA临床表现中的作用。我们使用聚合酶链反应（PCR）和聚合酶链反应-限制性片段长度多态性方法，对196例RA患者和来自塞尔维亚人群的132名健康个体组成的对照组进行基因分型。采用压痛关节数、肿胀关节数和28关节疾病活动评分（DAS28）对疾病活动进行前瞻性评估。在三个分析的单核苷酸多态性（SNP）的基因型和等位基因频率方面，患者组和对照组之间没有差异。我们的结果显示，在786TT/786CT与786CC基因型之间以及894GG/894GT与894TT基因型之间，所有三个分析的疾病严重程度参数均存在统计学显著差异。对于4a/b多态性，次要等位基因携带者的DAS28值显著较低。总之，我们的结果不支持所分析的eNOS基因多态性与RA易感性有关，但将它们与疾病活动相关联，并推测次要等位基因是更好临床病程的指标。
