Purpose: Inflammation is a key contributor to coronary heart disease (CHD). Sortilin is a sorting receptor and has been identified as a critical regulator of inflammatory response. Therefore, our study aimed to determine the link between circulating sortilin levels, proinflammatory cytokine levels, and the occurrence of CHD.
Patients and Methods: Our study included 227 CHD patients and 101 matched healthy individuals. Circulating serum levels of sortilin and proinflammatory cytokines, including IL-1β, IL-6 and TNF-α, were assessed by a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA). Linear regression and correlation analyses were used to estimate the associations between sortilin and proinflammatory cytokines. Moreover, six single-nucleotide polymorphisms (SNPs) spanning the sortilin and SORL1 genes were genotyped.
Results: Elevated levels of sortilin (P=0.027) and proinflammatory cytokines IL-1β (P=0.013), IL-6 (P=0.000) and TNF-α (P=0.010) were observed in CHD patients compared to those in healthy controls. Furthermore, sortilin levels were significantly positively correlated with IL-1β (r=0.252, P=0.0001), IL-6 (r=0.250, P=0.0001) and TNF-α (r=0.180, P=0.0064) levels. Notably, sortilin polymorphisms were revealed to be associated with the occurrence of CHD and varying sortilin levels. Subjects with the rs599839 AA risk genotype for CHD had significantly higher sortilin levels than those with the GG and GA genotypes (P=0.000); the same tendency was also observed in the levels of the proinflammatory cytokines IL-1β (P=0.003) and TNF-α (P=0.000). Similarly, GG carriers of rs464218 with increased sortilin levels were found to be at increased risk for CHD (P=0.014). The levels of IL-1β (P=0.025) and IL-6 (P=0.015) were also increased in these patients.
Conclusion: Our findings reveal that high sortilin levels may interact with inflammatory response to contribute to the occurrence of CHD. Considering that our clinical evidence suggests for the first time that sortilin involves in inflammatory response in CHD, the mechanistic role of sortilin in the progression of CHD deserves detailed investigation.

Keywords: sortilin, inflammation, SORL1, polymorphism, coronary heart disease


中文翻译：

---

Sortilin 与冠心病患者炎症的关系。

目的：炎症是导致冠心病（CHD）的关键因素。Sortilin 是一种分选受体，已被确定为炎症反应的关键调节因子。因此，我们的研究旨在确定循环分选蛋白水平、促炎细胞因子水平和冠心病发生之间的联系。
患者和方法：我们的研究包括 227 名 CHD 患者和 101 名匹配的健康个体。通过双抗体夹心酶联免疫吸附试验 (DAS-ELISA) 评估循环血清中分拣蛋白和促炎细胞因子的水平，包括 IL-1β、IL-6 和 TNF-α。线性回归和相关分析用于估计分拣蛋白和促炎细胞因子之间的关联。此外，对跨越 sortilin 和 SORL1 基因的六个单核苷酸多态性 (SNP) 进行了基因分型。
结果：与健康对照组相比，在 CHD 患者中观察到 sortilin (P=0.027) 和促炎细胞因子 IL-1β (P=0.013)、IL-6 (P=0.000) 和 TNF-α (P=0.010) 水平升高。此外，sortilin 水平与 IL-1β（r=0.252，P=0.0001）、IL-6（r=0.250，P=0.0001）和 TNF-α（r=0.180，P=0.0064）水平呈显着正相关。值得注意的是，sortilin 多态性被发现与 CHD 的发生和不同的 sortilin 水平有关。具有 rs599839 AA 风险基因型的 CHD 受试者的 sortilin 水平显着高于具有 GG 和 GA 基因型的受试者（P=0.000）；在促炎细胞因子IL-1β（P=0.003）和TNF-α（P=0.000）的水平上也观察到了同样的趋势。同样，发现具有增加的sortilin水平的rs464218的GG携带者患CHD的风险增加（P = 0.014）。
结论：我们的研究结果表明，高分选蛋白水平可能与炎症反应相互作用，从而导致 CHD 的发生。考虑到我们的临床证据首次表明 sortilin 参与 CHD 的炎症反应，sortilin 在 CHD 进展中的机制作用值得详细研究。

关键词： sortilin，炎症，SORL1，多态性，冠心病