Elevated interleukin-36γ and gene polymorphisms implicate novel risk in essential hypertension

Cytokines are crucial in regulating hypertension and vascular inflammation. The clinical significance of circulating IL-36γ levels and IL36G gene variants in relation to essential hypertension risk was assessed because IL-36γ has been associated with several cardiovascular diseases, while its role in essential hypertension is still unknown. Serum IL-36γ levels were determined by enzyme-linked immunosorbent assay, while IL36G polymorphisms were assessed by PCR-RFLP method in 264 patients with essential hypertension and 264 normotensive controls. Patients showed significantly elevated serum IL-36γ levels (p < 0.0001) when compared with the controls. Significant association between IL36G rs11690399 and rs11683399 polymorphisms and essential hypertension susceptibility were found through genotyping analysis, with combination genotypes (GT + TT) and (TG + GG) conferring an elevated risk of a disease. A 2.6-fold and a 1.9-fold increased risk of essential hypertension was observed to the T allele of rs11690399 and the G allele of rs11683399, respectively. Significantly higher levels of IL-36γ were associated with variant genotypes, suggesting a genotype-phenotype correlation. T-T and T-G were found to be a risk haplotype for essential hypertension by haplotype analysis. A causal relationship between increased IL-36γ and the risk of hypertension was shown by Mendelian randomization (OR = 1.0066; 95% CI: 1.0028-1.0104, p < 0.0001). A diagnostic performance for IL-36γ (AUC = 0.862) was found by ROC analysis, indicating its potential as a clinical biomarker. In conclusion, there is a significant association between essential hypertension and higher IL-36γ levels and IL36G polymorphisms. These results suggest that elevated circulatory IL-36γ may play a role in the pathophysiology of essential hypertension.