While a connection has been established between serum interleukin-6 (IL-6) levels and the IL-6 gene (− 174G/C) polymorphism in allergic diseases such as asthma, its specific association with severe asthma remains unexplored. This study examined the relationship between the IL-6 (− 174G/C) gene polymorphism and mild and severe asthma, focusing on its influence on type 2 inflammation. Our study comprised 98 patients with mild asthma and 116 with severe asthma. Additionally, we recruited 121 healthy participants to serve as controls for comparative analyses. The IL-6 gene (− 174G/C) polymorphism was assessed utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. In our study, the risk of mild asthma exhibited a significant fourfold increase in individuals with the GG genotype pattern compared to healthy controls, yielding an odds ratio (OR) of 4.4 (p < 0.001). Conversely, we found no significant correlation between the IL-6 − 174G/C gene polymorphism and severe asthma when compared to the healthy control group. However, a noteworthy pattern emerged when we compared subgroups of mild and severe asthma. The risk of severe asthma increased fivefold in individuals with the GC polymorphism pattern, with an OR of 4.99 (p < 0.001), while the likelihood of mild asthma showed a similar fourfold increase with the GG polymorphism pattern, OR = 4.4 (p < 0.001). Consequently, we observed a significantly higher frequency of the C allele in patients with severe asthma, whereas the G allele was more prevalent in individuals with mild asthma (p = 0.05). Additionally, the correlation between markers of type 2 inflammation and the dominant model of the IL-6 gene -174G/C polymorphism (CC + CG vs GG) revealed a significant increase in total serum immunoglobulin E (IgE), Blood Eosinophil Counts (BEC), and Fractional Exhaled Nitric Oxide (FeNO) levels in asthmatic patients with the CC + CG gene pattern compared to those with GG, with p-values of 0.04, 0.03, and 0.04, respectively. Furthermore, after adjusting for other risk factors, the likelihood of developing severe asthma increased from fourfold to eightfold, with an OR of 8.12 (p = 0.01) with (CC + CG) gene pattern. Other predictors for severe asthma included older age and childhood-onset disease (OR = 1.13 and 19.19, p < 0.001). Allergic rhinitis (AR) and nasal polyps (NP) also demonstrated a substantial association with an increased risk of severe asthma, with odds ratios of 5 and 32.29 (p = 0.01 and < 0.001), respectively. Additionally, elevated Body Mass Index (BMI), BEC, and FeNO were linked to severe asthma, with ORs of 1.11, 1.00, and 1.04, respectively (p = 0.04, 0.05, and 0.001). This study illuminated the intricate relationship between the IL-6 gene polymorphism, type 2 inflammation markers, and diverse risk factors in shaping asthma severity. As a significant association between the GG polymorphism of the IL-6 gene (− 174G/C) and mild asthma was found, while possessing at least one C allele, whether in a homozygous (CC) or heterozygous (CG) combination, independently predicts the likelihood of severe asthma.

中文翻译：

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IL-6-174G/C基因多态性与哮喘严重程度的关联：探讨血清总IgE、血嗜酸性粒细胞和FeNO作为2型炎症标志物的作用

虽然在哮喘等过敏性疾病中，血清白细胞介素 6 (IL-6) 水平与 IL-6 基因 (− 174G/C) 多态性之间存在联系，但其与严重哮喘的具体关联仍有待探索。本研究探讨了 IL-6 (− 174G/C) 基因多态性与轻度和重度哮喘之间的关系，重点关注其对 2 型炎症的影响。我们的研究包括 98 名轻度哮喘患者和 116 名重度哮喘患者。此外，我们还招募了 121 名健康参与者作为比较分析的对照。利用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法评估IL-6基因（− 174G/C）多态性。在我们的研究中，与健康对照相比，具有 GG 基因型模式的个体患轻度哮喘的风险显着增加四倍，比值比 (OR) 为 4.4 (p < 0.001)。相反，与健康对照组相比，我们发现 IL-6 – 174G/C 基因多态性与严重哮喘之间没有显着相关性。然而，当我们比较轻度和重度哮喘亚组时，出现了一个值得注意的模式。具有 GC 多态性模式的个体患严重哮喘的风险增加了五倍，OR 为 4.99 (p < 0.001)，而患有 GG 多态性模式的轻度哮喘的可能性也增加了四倍，OR = 4.4 (p < 0.001) ）。因此，我们观察到重度哮喘患者中 C 等位基因的出现频率显着较高，而 G 等位基因在轻度哮喘患者中更为常见 (p = 0.05)。此外，2 型炎症标志物与 IL-6 基因 -174G/C 多态性（CC + CG 与 GG）的显性模型之间的相关性揭示了总血清免疫球蛋白 E (IgE)、血液嗜酸性粒细胞计数 (BEC) 显着增加。 ) 和分数的呼出一氧化氮 (FeNO) 水平，CC + CG 基因模式的哮喘患者与 GG 患者相比，p 值分别为 0.04、0.03 和 0.04。此外，在调整其他危险因素后，患严重哮喘的可能性从四倍增加到八倍，(CC + CG) 基因模式的 OR 为 8.12 (p = 0.01)。严重哮喘的其他预测因素包括年龄较大和儿童期发病（OR = 1.13 和 19.19，p < 0.001）。过敏性鼻炎 (AR) 和鼻息肉 (NP) 也与严重哮喘风险增加显着相关，优势比分别为 5 和 32.29（p = 0.01 和 < 0.001）。此外，体重指数 (BMI)、BEC 和 FeNO 升高与严重哮喘相关，OR 分别为 1.11、1.00 和 1.04（p = 0.04、0.05 和 0.001）。这项研究阐明了 IL-6 基因多态性、2 型炎症标志物和影响哮喘严重程度的多种危险因素之间的复杂关系。