The impact of VKORC1-1639 G>A polymorphism on the maintenance dose of oral anticoagulants for thromboembolic prophylaxis in North India: A pilot study

Abstract

BACKGROUND:The dose requirements for oral anticoagulants in thromboembolic events are influenced by promoter polymorphism in the VKORC1 gene. However, limited data are available on the influence of the polymorphism in various Indian populations. The present study aimed at determining the relationship between the VKORC1-1639 G>A genotypes and maintenance doses of oral anticoagulants for therapeutically stable INR values in patients taking Acitrom after valve replacement surgery.MATERIALS AND METHODS:Fifty patients from the northern Indian region were genotyped for VKORC1-1639 G>A by polymerase chain reaction and restriction fragment length polymorphism. Means of the weight-normalized daily Acitrom dose were calculated for every patient.RESULTS AND DISCUSSION:The VKORC1 1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.1639G>A minor allele frequency in the study population (n = 50) was found to be 22%. The patients with a wild type genotype required the maximum drug dose as suggested for full functionality of the enzyme. Heterozygous patients were found to have an intermediate drug dose and the patients with a variant homozygous genotype had the minimum maintenance drug dose requirement. These findings are in concurrence with the effect of the promoter polymorphism on vitamin K epoxide reductase activity.CONCLUSION:The VKORC1-1639 G>A status can be indicative of establishing the therapeutic dose of oral anticoagulants in Indian patients.

Creating and validating a warfarin pharmacogenetic dosing algorithm for Colombian patients

“… 35 Moreover, this variant has been related to a quantitative change in VKORC1 expression. 36 This finding is consistent with a reduced warfarin maintenance dose in patients carrying the VKORC1 -1639A allele. 35 …”

The effect of CYP2C9*2, CYP2C9*3, and VKORC1-1639 G>A polymorphism in patients under warfarin therapy in city of Kermanshah

“…The CYP2C9*2 , CYP2C9*3 , and VKORC1-1639 G>A polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The used primers were as follows: CYP2C9*2 forward: 5´-GTA TTT TGG CCT GAA ACC C-3´, CYP2C9*2 reverse: 5´ -GGC CTT GGT TTT TCT CAA CTC-3´( 16 ); CYP2C9*3 forward: 5´-TGC ACG AGG TCC AGA GGT AC-3´, CYP2C9*3 reverse: 5´-ACA AAC TTA CCT TGG GAA TGA GA-3´( 17 ); VKORC1-1639 G>A forward: 5´-GCC AGC AGG AGA GGG AAA TA-3´, VKORC1-1639 G>A reverse: 5´-AGT TTG GAC TAC GGT GCC T-3´( 18 ). The PCR reaction consisted of buffer 10× (100 mM tris-HCl, 500 mM KCl, 50 mM MgCl 2 , pH 8.3), 0.2 mM dNTPs, 200 ng template DNA, and 1U AmpliTaq DNA polymerase.…”

Follow-up and management of valvular heart disease patients with prosthetic valve: a clinical practice guideline for Indian scenario

“…Warfarin dose titration algorithms have been established which can provide a base for genetic testing in India [ 132 , 133 ]. Many of the studies have earlier shown that around 75–80% of the Indian population carries VKORC1 - 1639GG (rs9923231) genotype, which is associated with high dose requirement [ 129 , 134 – 136 ]. A study by Rathore S et al has shown that the VKORC1 - 1639 G > A status can be indicative of establishing the therapeutic dose of OATs in Indian prosthetic valve patients [ 136 ].…”

“…Many of the studies have earlier shown that around 75–80% of the Indian population carries VKORC1 - 1639GG (rs9923231) genotype, which is associated with high dose requirement [ 129 , 134 – 136 ]. A study by Rathore S et al has shown that the VKORC1 - 1639 G > A status can be indicative of establishing the therapeutic dose of OATs in Indian prosthetic valve patients [ 136 ]. When inter-individual dose variability of acenocoumarol in the Indian patients with CYP2C9 and VKORC1 gene polymorphisms were evaluated, lower dose requirements for carriers of the studied polymorphisms had been identified and there was considerable variability in the dose requirements of carriers and non-carriers of the variant alleles [ 137 ].…”