HMGB1 gene polymorphism is associated with hypertension in Han Chinese population

High-mobility group box 1 protein (HMGB1) acts as a proinflammatory cytokine by activating pattern recognition receptors (PRRs), including Toll-like receptor 4 (TLR4) and the receptor of AGE (AGER) with oxidative injury. Animal study proved that HMGB1 contributed to the pathogenesis of experimental pulmonary hypertension (HT) via activation of TLR4. The aim of this study is to test whether HMGB1 harbor genetic susceptibility to HT in a Chinese population.

A case-control study comprising 2012 HT cases and 2210 controls was used to evaluate the association of three tagging single nucleotide polymorphism (tagSNPs) in HMGB1 gene with HT and blood pressure. Logistic regression model was used to adjust confounding factor for HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes in cases and controls.

Single locus analysis showed that there was no statistical association of three tagSNPs with HT after adjustment for the covariates. Further stratification analysis found that rs2249825 was significantly associated with HT in ≥55 years groups, ORs (95% CI) of additive model and dominant model were 1.208 (1.029-1.417) and 1.212 (1.020-1.441), and p values were 0.021 and 0.029, respectively. Quantitative trait analysis indicated that DBP had a linear decrease with the variations of rs2249825 in both untreated HT group (p=0.002) and control group (p=0.034) respectively.

Our finding suggests that rs2249825 of HMGB1 genetic polymorphisms are significantly associated with HT and diastolic blood pressure, and the genetic effect on HT is modulated by age.