TRIB3 rs6037475 is a potential biomarker for predicting felodipine drug response in Chinese patients with hypertension.

Abstract

BackgroundOur previous studies have found that single nucleotide polymorphisms (SNPs) of tribbles homolog 3 (TRIB3) are related to the hypotensive effects of calcium-channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors. In this study, we aimed at exploring and validating the effect of TRIB3 polymorphism on antihypertensive drugs responses.MethodsA total of 830 hypertensive patients, who were administered with open-labeled hydrochlorothiazide (12.5 mg once daily) and randomly assigned to off-labeled felodipine (5 mg) or a matched placebo combination treatment (1:1), were selected from the Felodipine Event Reduction (FEVER) study. A strategy of screening 259 samples and validating the remaining 531 samples was implemented. Four functional SNPs were selected (rs2295490, rs11470129, rs4815567 and rs6037475 in TRIB3). A mixed linear model was performed to analyze the effects of TRIB3 SNPs on antihypertensive drugs responses.ResultsWe found that TRIB3 rs6037475 CC genotype was associated with a reduction of diastolic blood pressure (DBP) (P=6.3×10−3) in the felodipine treatment group of screening set, and was also associated with a reduction of systolic blood pressure (SBP) (P=0.021), DBP (P=6.0×10−3) and mean arterial pressure (MAP) (P=0.021) in the felodipine treatment group of the validation set. As for the reductions influenced by the rs2295490, rs11470129 and rs4815567 genetic variations, however, the adjusted P-value did not reach statistical significance. Combined screening and validation set analysis found that patients with TRIB3 rs6037475 CC genotype had a significant higher mean SBP, DBP and MAP than those with TT genotype in the felodipine treatment group (CC vs. TT −10.2±0.74 vs. −17.8±0.21, P=7.8×10−3; −4.6±0.50 vs. −10.2±0.23, P=3.0×10−4; −6.5±0.54 vs. −12.7±0.14, P=3.0×10−4, respectively).ConclusionsThese results suggest that TRIB3 rs6037475 genetic variation can be useful as a bio-marker for predicting felodipine drug response in Chinese patients with hypertension.