Impact of GGCX polymorphisms on warfarin doserequirements in atrial fibrillation patients

Abstract

Background/aim: Warfarin is a common anticoagulant with large interindividual differences and a narrow therapeutic range. The polymorphisms of gamma-glutamyl carboxylase (GGCX) are important genetic factors for warfarin dose requirements. Materials and methods:Polymerase chain reaction and direct sequencing methods were used to detect the GGCX rs699664 genotype in 215 atrial fibrillation (AF) patients with warfarin administration. The effects on warfarin dose by different genotypes were analyzed. A warfarin dosing algorithm was developed based on age, height, CYP2C9, VKORC1, and GGCX genotype. Results:In 215 AF patients, there were 104 cases of wild-type GG genotype (48.4%), 92 cases of GA genotype (42.8%), and 19 cases of AA genotype (8.8%). Patients with the GGCX rs699664 A allele (GA or AA genotypes) needed higher warfarin doses than those with the GG genotype (P < 0.05). A warfarin dosing algorithm showed that age, height, CYP2C9, VKORC1, and GGCX genotype were the best variables for estimating warfarin dose (R2 = 41.2%). Another independent cohort of 60 AF patients showed a significant linear correlation between predicted warfarin maintenance dose and actual dose (R = 0.660, P < 0.01). Conclusion:AF patients with the GA and AA genotypes in GGCX rs699664 required significantly higher warfarin doses. GGCX rs699664 is a potential predictor for the warfarin dose of AF patients.

Impact of VKORC1, CYP2C9, CYP1A2, UGT1A1, and GGCX polymorphisms on warfarin maintenance dose: Exploring a new algorithm in South Chinese patients accept mechanical heart valve replacement

“…Therefore, we strongly suggest that it is inappropriate to sequence VKORC1 for multiple loci to avoid unnecessary resource wastage. Furthermore, our study found that the effect of GGCX rs699664 on the daily stable dose of warfarin was statistically significant, which is consistent with the findings of Jiang et al [ 19 ] We first retained this SNP in the final model after stepwise screening, which accounted for 2% of the individual differences. GGCX rs699664 may be an important predictor in the warfarin dose algorithm, but further research is needed in the future.…”

“…For CYP1A2 rs2069514, our results were inconsistent with those of Liu et al, [ 16 ] which may be due to the fact that their study subjects were from the Northern Chinese population. Regarding UGT1A1 rs887829, Thai scholars reported results that were consistent with ours and also confirmed its lack of contribution to the model, [ 19 ] which was contrary to the findings of Korean scholars whose research also focused on Asians [ 20 ] and the specific reasons remain to be discussed.…”

“…[11,17,18] The SNP rs699664 affects the dose of warfarin. [19] Uridine diphosphate glucuronyl transferase, encoded by UGT1A1, catalyzes the second-phase biotransformation of warfarin, [20,21] and its SNP rs 887829 accounts for approximately 5.5% of individual differences. [22] Studies on the predictive modeling of warfarin administration involving these 3 genes are still lacking.…”

Gene Polymorphisms Associated with Atrial Fibrillation

“…. In this study, CT and TT genotypes of GGCX rs2592551 gene polymorphism were found to be associated with higher warfarin dose requirements than CC genotype in patients with AF [14,15]. It is presented primer sequences that used to determine GGCX rs699664, rs2592551 gene polymorphisms in Table 6.…”