Mendelian randomisation analysis suggests that plasma interleukin-6 is raised in hypertension but does not cause its development

Abstract

Introduction: Interleukin-6 (IL-6) plays a central role in inflammation and insulin resistance as well as atherogenesis. We investigated the associations of plasma IL-6 and its genetic variants with hypertension in both cross-sectional and prospective study designs. Methods: Plasma IL-6 was measured in 648 normotensive and 294 hypertensive subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000-2004 and three tagging SNPs in the IL-6 gene (IL6) were genotyped. Among subjects normotensive in CRISPS-2, 515 subjects were followed up in CRISPS-3 in 2005- 2008 and 100 of them had developed hypertension. Results: Plasma IL-6 correlated with systolic blood pressure (r=0.128, P<0.001), pulse pressure (r=0.144, P<0.001), and mean arterial pressure (r=0.086, P=0.008). Hypertensive subjects have significantly higher plasma IL-6 level after adjusting for age and sex (geometric mean [95% CI]=0.60 [0.54-0.65] vs 0.47 [0.44-0.50] pg/mL, P=0.021). In stepwise logistic regression, plasma IL-6 was associated with hypertension in women (P=0.004), but not in men. The SNP rs1800796 was associated with plasma IL-6 (beta= –0.098, P=0.002) in stepwise linear regression. However, this SNP was not associated with hypertension or blood pressure. Among subjects normotensive in CRISPS-2, plasma IL-6 was not associated with the development of hypertension in CRISPS-3. Conclusion: Elevated plasma IL-6 is associated with hypertension, especially in women. Plasma IL-6 is influenced by the SNP rs1800796. However, this SNP is not associated with hypertension, suggesting that hypertension is caused by other factors that elevate plasma IL-6. Acknowledgement: This study was funded by Hong Kong Research Grant Council grants (HKU7229/01M and HKU7626/07M) and the Sun Chieh Yeh Heart Foundation.