Association Study of Common Variants in PFN1 With Hypertension in a Han Chinese Population: A Case-Control Study and A Follow-up Study.

BACKGROUND: Animal researches reported that the dysfunction of profilin1 (PFN1) was involved in the physiological arterial stiffness and vascular remodeling linking to the etiology of hypertension (HT). This study mainly aims at evaluating the association of PFN1 and HT in a Han Chinese population.

METHODS: A case-control study consisted of 2,012 HT cases and 2,210 controls was conducted and 2,116 participants from the healthy controls were further followed up for average 5.01 years. Logistic and Cox regression models were applied to evaluate the association of 4 tag single nucleotide polymorphisms (SNPs) of PFN1 and ENO3 with HT.

RESULTS: There was no significant association of the 4 SNPs between HT cases and controls even after adjustment for confounding factors (P > 0.05). Haplotype analysis did not identify any significant haplotype with HT. There were no statistical difference of systolic blood pressure (BP) and diastolic BP among different genotypes in antihypertensive-treated group and untreated group. In follow-up population, there was no significant association of candidate SNPs with HT even after adjustment for covariates (all P > 0.05). Of note, the plasma profilin1 level of HT cases was significantly higher than that of control subjects (P = 0.011). The profilin1 levels of controls significantly decreased with variation of rs238243 at PFN1 (P = 0.041), and the profilin1 levels of HT cases increased with variation of rs238238 at ENO3 (P = 0.004).

CONCLUSIONS: Our results suggest that HT cases displayed an elevated plasma profilin1. Variants of rs238243 and rs238238 might regulate profilin1 expression by epigenetic modification and indirectly affects the susceptible threshold of HT.