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Association of IL-6 promoter polymorphism hotspots (− 174G/C and − 572G/C) with cardiovascular disease risk factors

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Abstract

Background

Cardiovascular disease (CVD) is the leading cause of death globally, despite the recent advancements in clinical research. Early diagnosis of CVD and prevention of future complications are important for the management of CVD. In the present study, we determined the genotypic linkage of interleukin-6 (IL-6) promoters with the clinical, biochemical, and inflammatory markers of CVD in the Saudi population.

Materials and methods

The study consisted of 89 patients (male and female) with CVD who were admitted at the King Abdulaziz university hospital, Jeddah, Saudi Arabia. The biochemical parameters were evaluated using an automated chemistry analyzer, and inflammatory markers were measured using specific enzyme-linked immunosorbent assay (ELISA) kits. For genotypic analysis, Sanger sequencing was performed. We observed a statistically significant association (p < 0.05) between GG (66.29%), GC (30.34%), and CC (3.37%) genotypes at the − 174G/C (rs1800795) hotspot and neopterin levels. However, the genotypes at the − 572G/C (rs1800796) hotspot did not show any association with age, gender, obesity, diabetes, hypertension, dyslipidemia, smoking, and coronary artery status. In addition, no significant association was observed with biochemical and inflammatory markers, namely fasting blood sugar, glycated hemoglobin A1c, creatinine, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, IL-6, and C-reactive protein. The comparison between different possible genotypic groups and CVD risk factors showed a statistically significant (p < 0.05) association between the male gender and HDL with GG, rs1800795 group vs. GC, rs1800796 group. Similarly, neopterin level was also found to be significantly (p < 0.05) associated with the genotypes GC, rs1800795, and GG, rs1800796. Additionally, the male gender (p < 0.01), age (p < 0.05), serum creatinine (p < 0.001), and neopterin (p < 0.05) were found to be significantly associated with GG, rs1800795 + GG, rs1800796, GC, rs1800795 + GC, and rs1800796 GC.

Conclusion

The direct association of neopterin level with IL-6 promoter polymorphism at − 174G/C (rs1800795) hotspot indicated the role of inflammation in CVD pathogenesis in the Saudi population.

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Acknowledgements

This project was funded by the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, under Grant Number (G: 332–141–1442). The authors, therefore, acknowledge with thanks DSR technical and financial support.

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Authors and Affiliations

Authors

Contributions

S.T, T.A.Z and N.R.J performed the experiments. M.S. was involved in the analysis of the sequenced data. All authors reviewed the final draft of the manuscript.

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Correspondence to Shams Tabrez.

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The author(s) declare that there is no conflict of interest regarding the publication of this article.

Ethical approval

The current study was conducted in compliance with the Declaration of Helsinki, and the study protocol was approved by the institutional ethical committee (Reference No. 84–16).

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Written and properly informed consent was acquired from each individual involved in the study before the commencement of sample collection.

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Tabrez, S., Jabir, N.R., Zughaibi, T.A. et al. Association of IL-6 promoter polymorphism hotspots (− 174G/C and − 572G/C) with cardiovascular disease risk factors. Mol Biol Rep 49, 2265–2272 (2022). https://doi.org/10.1007/s11033-021-07048-8

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