Wenxiu Han,1 Zhijie Wei,2 Hailiang Zhang,1 Chunmei Geng,1 Ruili Dang,1 Mengqi Yang,1 Jun Zhang,3 Changshui Wang,1 Pei Jiang1
1Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272011, People’s Republic of China; 2Department of Medical Administration, Jining First People’s Hospital, Jining Medical University, Jining 272011, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, People’s Republic of China
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
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