Personalized warfarin treatment based on the PITX2 single nucleotide polymorphism rs6843082.

Objective: To explore the effect of PITX2 gene rs6843082 single nucleotide polymorphism on the efficacy and adverse reactions of warfarin in patients with atrial fibrillation and hypertension, and to provide a theoretical basis for individualized warfarin treatment.

Methods: Data on 97 patients with atrial fibrillation and hypertension treated in our hospital were collected from September, 2018 to December, 2019. PCR and SNP genotyping techniques were used to measure the genotype at the rs6843082 locus (pituitary homeobox 2, PITX2) using DNA from the peripheral blood cells of all patients. We compared the efficacy of warfarin and the incidence of adverse reactions in patients of different genotypes.

Results: (1) Among 97 subjects, 58 cases (59.79%), 32 cases (32.99%) and 7 cases (7.22%) of PITX2 (rs6843082) genotypes GG, GA and AA were identified respectively. The G and A allele frequencies were 76.29% and 23.71%, respectively. (2) After all patients took warfarin to achieve the standard, the GA group and AA group's time to achieve the standard was significantly longer than that of the GG group (<0.05). The difference was not statistically significant among groups (>0.05). Compared with the GG group, the maintenance dose of the AA group was increased (<0.05). (3) Compared with the GG and the GA group, the probability of bleeding events was higher in the AA group (<0.05). (4) There was no difference in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV) group among GG, GA and AA groups (>0.05). Compared with the GG group, left ventricular ejection fraction (LVEF) of the AA group was significantly reduced (<0.05). (5) The mortality rates of the GG, GA, and AA groups were 15.51%, 12.50% and 22.57%, respectively, at the end of 120 d follow-up.

Conclusion: Our findings show that rs6843082 SNP leads to the warfarin dose response differences that were observed in patients with atrial fibrillation and hypertension. Genotyping patients for rs6843082 before initiating warfarin treatment may optimize the treatment response and reduce bleeding incidence.