Key result
VKORC1-1639 G/A AG+GG carriers and 1173 C/T CT carriers required significantly higher warfarin maintenance doses than AA and TT carriers, respectively (P<0.001).
Why the study?
Do VKORC1 genetic polymorphisms affect warfarin maintenance dose requirements in Chinese Han patients undergoing cardiac valve replacement?
Cohort (n=298)
Do VKORC1 genetic polymorphisms affect warfarin maintenance dose requirements in Chinese Han patients undergoing cardiac valve replacement?
p-value: p=<0.001
VKORC1 gene polymorphisms (-1639 G/A and 1173 C/T) are significant genetic determinants of warfarin maintenance dose requirements in Chinese Han patients following cardiac valve replacement.
Supports VKORC1 genotyping for warfarin dosing; leaves open need for prospective trials before practice change.
BACKGROUND VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1-1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. MATERIAL AND METHODS A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1-1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. RESULTS Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all P<0.05). Warfarin maintenance dose in VKORC1-1639 G/A AG + GG carriers was obviously higher than in AA carriers (P<0.001). As compared with patients with TT genotype in VKORC1 1173 C/T, warfarin maintenance dose was apparently higher in patients with CT genotype (P<0.001). Linear regression analysis revealed that gender, operation method, method for heart valve replacement, as well as VKORC1-1639 G/A and 1173 C/T gene polymorphisms were significantly related to warfarin maintenance dose (all P<0.05). CONCLUSIONS VKORC1 gene polymorphisms are key genetic factors to affect individual differences in warfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose.
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Yan et al. (2015) conducted a cohort in Cardiac valve replacement requiring warfarin (n=298). VKORC1 genetic polymorphisms (-1639 G/A, 1173 C/T, 497 T/G) vs. Reference genotypes (AA for -1639 G/A, TT for 1173 C/T) was evaluated on Warfarin maintenance dose requirement (p=<0.001). VKORC1-1639 G/A AG+GG carriers and 1173 C/T CT carriers required significantly higher warfarin maintenance doses than AA and TT carriers, respectively (P<0.001).
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