Association of Interleukin-6 Genetic Polymorphisms (rs1800795, -174C > G and rs1800796, -572G > C) With Risk of Essential Hypertension in the Chinese Population

Huan Ren; Zhen Guo; Wen-Jie Qin; Zhi-Ling Yang

doi:10.7759/cureus.46334

Association of Interleukin-6 Genetic Polymorphisms (rs1800795, -174C > G and rs1800796, -572G > C) With Risk of Essential Hypertension in the Chinese Population

Cureus. 2023 Oct 1;15(10):e46334. doi: 10.7759/cureus.46334. eCollection 2023 Oct.

Authors

Huan Ren¹, Zhen Guo², Wen-Jie Qin¹, Zhi-Ling Yang¹

Affiliations

¹ Pharmacy, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, CHN.
² Genetics, Hunan Provincial Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha, CHN.

Abstract

Background Interleukin-6 (IL-6) plays a critical role in essential hypertension (EH) and cardiovascular disease. Evidence suggests two hotspot single nucleotide polymorphisms (SNPs) of the IL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) might be associated with the susceptibility of EH. However, no consensus has yet been established. Thus, we aimed to investigate the potential association between IL-6 gene polymorphisms and the risk of EH based on a case-control study in a Chinese population. Materials and methods A total of 479 subjects (272 healthy controls and 207 EH patients) were randomly enrolled in our study. After extracting the genomic DNA, two SNPs of the IL-6 gene (rs1800795, -174C > G and rs1800796, -572G > C) were genotyped to analyze the potential association between these genetic variants and EH risk. Multiple genetic models were performed to investigate the strength of association by calculating the odds ratio (OR) and 95% confidence interval (95% CI). The potential effect of SNPs on gene expression was evaluated using expression quantitative trait loci (eQTL) analysis. Results The genotyping findings of IL-6 rs1800795, -174C > G polymorphism showed three study participants with CG genotype and 204 with GG genotype in the EH patients. The IL-6 -174C > G polymorphism was significantly associated with EH risk (P = 0.046) and conferred a reduced risk of EH development (OR = 0.99, 95%CI = 0.97-1.00). Conversely, no substantial association between IL-6 rs1800796, -572G > C polymorphism and the risk of EH was found in all genetic models (P > 0.05). Moreover, the eQTL analysis indicated that the -174C > G polymorphism was significantly associated with gene expression of IL-6 (P = 0.006), and the G allele corresponded to a reduced IL-6 gene expression (Beta = -0.397). Compared with -174C > G, the -572G > C polymorphism was not found to be significantly associated with IL-6 gene expression (Beta = -0.120, P = 0.560). Conclusions Our findings provide evidence that the rs1800795, -174C > G polymorphism can affect the expression levels of IL-6, and the risk of EH occurrence. However, the rs1800796, -572G > C polymorphism does not regulate the IL-6 gene expression levels and the susceptibility of EH.

Keywords: essential hypertension; genetic polymorphism; inflammatory factor; interleukin-6; single nucleotide polymorphism.

Grants and funding

This study was supported by grants from Changsha Natural Science Foundation (kq2208126), the National Natural Science Foundation of China (No. 82104309), Natural Science Foundation of Hunan Province (No. 2021JJ40639), Excellent Youth Project of Hunan Natural Science Foundation (No. 2023JJ20042), and Changsha Outstanding Innovative Youth Training Plan (No. kq2209024).