IL-12B Gene Polymorphisms and IL-12 p70 Serum Levels Among Patients with Rheumatoid Arthritis
IL-12B Gene Polymorphisms and IL-12 p70 Serum Levels Among Patients with Rheumatoid Arthritis
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DOI：
10.1111/sji.12514
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发表时间：
2017-02-01
影响因子：
3.7
通讯作者：
Olesinska, M.
中科院分区：
文献类型：
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作者：
Paradowska-Gorycka, A.;Sowinska, A.;Olesinska, M.
类风湿关节炎（RA）是一种自身免疫性疾病，细胞因子基因的不同多态性在其发病机制中起着重要作用。IL-12现在被认为是调节Th1和Th2细胞之间平衡的关键细胞因子。我们研究了IL-12B基因单核苷酸多态性（rs3212227 （A/C）和rs17860508 (CTCTAA/GC)）在RA遗传易感性和疾病严重程度中的作用。采用PCR-RFLP方法和高分辨率熔融分析对634例高加索RA患者和341例健康对照者进行了研究。ELISA法检测血清IL-12细胞因子水平。在每个检查组中，基因型频率没有偏离HWE。在共显性和隐性模型中，RA患者rs3212227 CC基因型的频率均高于健康对照组，差异有统计学意义（P = 0.037; P = 0.04）。rs3212227 C等位基因的频率也有相似的趋势（P = 0.07）。RA组血清IL-12水平显著高于对照组（P < 0.0001）。我们观察到血清IL-12水平升高与压痛和肿胀关节数量增加、ExRA存在以及血红蛋白、CRP和PLT水平升高相关。RA合并高血压患者血清IL-12水平升高。目前的研究结果表明，在波兰人群中，IL-12p40 + 1188A/C多态性以及IL-12p70蛋白水平可能与RA有关。
Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. IL-12 is now recognized as a critical cytokine in terms of regulating the balance between Th1 and Th2 cells. We investigated the role of single nucleotide polymorphisms (SNPs) (rs3212227 (A/C) and rs17860508 (CTCTAA/GC)) of the IL-12B gene in the genetic susceptibility to RA and in the severity of the disease. Six hundred and thirty-four Caucasian RA patients and 341 healthy matched controls were studied using PCR-RFLP method and high-resolution melting analysis. Concentration of IL-12 cytokine level in serum was evaluated using ELISA. The genotype frequency did not deviate from HWE in each examined group. Frequencies of the rs3212227 CC genotype were statistically higher in patients with RA compared with the healthy control group in both codominant and recessive models (P = 0.037; P = 0.04, respectively). The frequency of rs3212227 C allele also showed similar tendency (P = 0.07). IL-12 level in serum was significantly higher in RA group compared with control (P < 0.0001). We observed that increased IL-12 serum level was correlated with higher number of tender and swollen joints, ExRA presence and higher levels of haemoglobin, CRP and PLT. Also higher IL-12 level in serum was observed within RA patients with hypertension. Present findings indicated that IL-12p40 + 1188A/C polymorphism as well as IL-12p70 protein levels may be associated with RA in the Polish population.