Journal of Pharmacogenomics & Pharmacoproteomics

Abstract

Polymorphisms in Genes Encoding Metalloproteinase 9 and Lymphotoxin-Alpha can Influence Warfarin Treatment

Jéssica B Borges, Thiago DC Hirata, Alvaro Cerda, Cristina M Fajardo, Raony CC Cesar, João ID França, Jéssica C Santos, Hui-Tzu L Wang, Lara R Castro, Marcelo F Sampaio, Rosario DC Hirata and Mario H Hirata

Objectives: Warfarin treatment is influenced by environmental and genetic factors. The influence of polymorphisms in genes encoding metalloproteinase 9 (MMP9), lymphotoxin-alpha (LTA) andTNFSF14 (LIGHT), related to the inflammatory process of coronary artery disease, on warfarin dose and time to reach target was investigated in this study. Methods: Outpatients on warfarin treatment (n=227), 20 to 92 years, were enrolled at the Institute Dante Pazzanese of Cardiology (IDPC). Genomic DNA was obtained from peripheral whole blood to evaluate MMP9 rs17576 (Gln279Arg, A>G), LTA rs1041981 (Thr60Asn, C>A) and rs909253 (c.252T>C) and TNFSF14rs2291668 (c.147C>T) and rs344560 (Lys214Glu, G>A) polymorphisms by pyrosequencing in Q24PyroMark. Results: The patients carrying MMP9 rs17576GG genotype were more likely to require a lower warfarin weekly dose (OR: 2.73, 95% CI: 1.01-7.41, p=0.048). Also, LTA rs909253 variant was associated with a longer time to reach the target international normalized ratio (INR) (OR: 1.98, 95% CI: 1.02-3.86, p=0.043). Age was inversely correlated with the target INR (r=-0.387, p<0.001), and dose was directly correlated with time to reach target INR (r=0.244, p<0.001). Conclusion: MMP9 rs17576 variant may have an important influence on warfarin weekly dose, and that LTA rs909253 polymorphism may also influence the time to reach the target INR.