Influence of <i>VKORC1</i> and <i>CYP2C9</i> Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves

Kalpana, S; Bharath, G; Manjunath, Cholenahalli Nanjappa; Christopher, Rita

doi:10.1177/1076029616655617

Cited by 11 publications

(13 citation statements)

References 25 publications

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“…Among Southeast Asian countries, Vietnamese had close CYP2C9*3 wild-type allele distribution to Thais, Malaysian, Indonesian. However, variant alleles of VKORC1-1173 and -1639 in these countries were in range of 64 to 70 %, lower than that of Vietnamese (85.3 and 92.7 %, respectively) [14,18].…”

Section: Discussionmentioning

confidence: 69%

“…These distributions of CYP2C9*3, VKORC1-1173 and VKORC1-1639 allele in Vietnamese population in this study were similar to these of East Asia people, for example Han-Chinese (95; 81.2 and 90 %), Japanese (95.8; 81.9 and 90.3 %), Korea (90.8; 85.5 and 92 %) and Taiwan (95.4; 80.5 and 89.0 %), respectively [18]. However, this prevalence was significantly different with other populations, including South, West and Central Asian, Caucasians, South American where the wild-type allele of CYP2C9*3 (60 -85 %) and variant alleles of VKORC1-1173 and VKORC1-1639 (14 -56 %) were rather lower [14]. Among Southeast Asian countries, Vietnamese had close CYP2C9*3 wild-type allele distribution to Thais, Malaysian, Indonesian.…”

Section: Discussionmentioning

confidence: 90%

“…In 2013, Buzoianu et al reported that both CYP2C9*3 and VKORC1-1639 G>A variant alleles played an important role on acenocoumarol dose response of Romanian patients [15]. Other studies on the North and the South Indian patients with mechanical heart valve showed that the patients carried the combination of variant alleles of CYP2C9*2, *3 and VKORC1-1639 and -1173 received lower dose of acenocoumarol treatment to reach INR from 2.5 to 3.0 [11,14]. Similar conclusions were proposed by Hungarian [12], Lebanese [13], Romanian [15], Pakistani [20].…”

Section: Discussionmentioning

confidence: 99%

“…Among various SNPs, CYP2C9*2, *3 and VKORC1-1173 and -1639 are well known for high prevalence and association with anticoagulant drug dose. The studies in Hungarian, Romanian, Lebanese, South Indian people demonstrated that patients with variant allele of CYP2C9*2, *3 and VKORC1*2 required low dose of acenocoumarol and had high risk of blood bleeding than people who carried wildtype allele [12][13][14][15]. Other studies also reported the impact of CYP2C9, VKORC1 on warfarin dosage response in Han-Chinese population [16,17].…”

Section: Introductionmentioning

confidence: 99%

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VKORC1 and CYP2C9*3 Polymorphisms and Their Impacts to Acenocoumarol Dosage in Vietnamese Heart Valve Replacement Patients

Pham

Nhung

Ta³

et al. 2019

Walailak J Sci & Tech

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Acenocoumarol therapy has been widely used for heart valve replacement (HVR) patients in Vietnam to improve dose management of this drug. The variety of responses among patients to this drug are driven by genetic background. Hence, aim of the study is to explore the relation between acenocoumarol dosages and genetic polymorphisms of CYP2C9*3, VKORC1-1173 C>T and VKORC1-1639 G>A genes. One hundred fifty HVR patients was enrolled in this study. Blood samples were collected and analyzed using PCR and Sanger’s sequencing. The result showed that there was no variant homozygous genotype (CC) of CYP2C9*3 observed, whereas wild-type (AA) and heterozygous (AC) were most abundant with 95.3, and 4.7 %, respectively. In contrast, variant homozygous genotypes of VKORC1-1173 C>T and -1639 G>A accounted for 70.7 and 87.3 % of Vietnamese HVR patient population while wildtype homozygous was not seen. Interestingly, there was significant difference in acenocoumarol doses between 2 genotypes of VKORC1-1173 C>T, but this result was not observed for CYP2C9*3. Patients with the variant homozygous genotype of VKORC1-1173 C>T have the lower dose of acenocoumarol in comparison with heterozygous genotype (p = 0.001). In conclusion, polymorphism of VKORC1-1173 C>T not CYP2C9*3 contributeseemed to relate to acenocoumarol dose responses of Vietnamese HVR patients.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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VKORC1 and CYP2C9*3 Polymorphisms and Their Impacts to Acenocoumarol Dosage in Vietnamese Heart Valve Replacement Patients

Pham

Nhung

Ta³

et al. 2019

Walailak J Sci & Tech

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“…A few studies from South Indian states have published data regarding the VKORC1 (−1639G>A) rs9923231 polymorphism and its effect on daily warfarin dose requirement 11, 12, 13, 14, 15, 16. Meanwhile, other studies on South Indian populations have also reported allele and genotypic frequencies without accessing association with dosage requirements 17, 18, 19, 20.…”

Section: Introductionmentioning

confidence: 99%

Value of VKORC1 (−1639G>A) rs9923231 genotyping in predicting warfarin dose: A replication study in South Indian population

Harikrishnan

Koshy

Subramanian

et al. 2018

Indian Heart Journal

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ObjectiveWarfarin is the most commonly prescribed oral anticoagulant, although having a narrow therapeutic index and wide interindividual variability. The aim of this study was to replicate the utility of VKORC1 (−1639G>A) rs9923231 genotyping in predicting the mean daily dose and to evaluate its ability to categorize warfarin-treated patients to high-, intermediate-, or low-dose categories in the South Indian population.Materials and methodsA cohort of 222 warfarin-treated patients was genotyped using restriction fragment length polymorphism method. The influence of the rs9923231 polymorphism on the variations in the mean daily dose was compared using one-way analysis of variance and linear regression analysis. Discriminatory ability of the rs9923231 polymorphism to group the patients into ordered dose categories was assessed by estimating the proportional odds ratios using the ordered logit regression analysis.ResultsThe frequency of AA genotype and A allele in the study sample was found to be 1.8% and 9.23%, respectively, which was similar to reports from other South Indian populations. The mean daily dose required to achieve the optimum international normalized ratio was significantly lower in AA homozygous genotype carriers (3.99 ± 1.67 mg/day) and GA heterozygous (4.26 ± 1.57 mg/day) compared to the GG genotype carriers (5.51 ± 2.13 mg/day), p = 0.003. The A allele carriers (GA+AA genotypes) had a 3.23 higher odds of being grouped as a low-dose requiring category compared to non-carriers (95% CI 1.49–6.98, p = 0.003).ConclusionsThese preliminary results strongly support the use of VKORC1 (−1639G>A) rs9923231 polymorphism for genetically guided initial warfarin dosing in South Indian patients with heart valve replacements.

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Association between polymorphisms of VKORC1 and CYP2C9 genes with warfarin maintenance dose in a group of warfarin users in Birjand city, Iran

Fereidouni

Moossavi

Kazemi

et al. 2018

J of Cellular Biochemistry

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Warfarin is the cardinal anticoagulant drug prescribed around the world. Due to stochastic bleeding in patients, it is essential to adjust the dose for every individual. The aim of the present study was to evaluate the frequency of CYP2C9 and VKORC1 gene polymorphisms and their association with warfarin maintenance dose in a sample of cardiovascular patients in Birjand, South-Khorasan province of Iran. Patients with a history of cardiovascular disorders who take warfarin daily were selected. CYP2C9 and VKORC1 gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in all participants. A total of 114 patients (mean age: 52.7 ± 14.9 years, M/F ratio: 0.76) participated in this study. Regarding CYP2C9 gene polymorphisms, the most frequent genotype was 1*/1* (80.4% in females and 62.5% in males). The frequency of 1*/2* and 2*/2* variants was 13% and 6.5% in females and 25% and 12.5% in males, respectively. The frequency of VKORC1 gene (1639 G > A), was 31.5%, 39.5%, and 29% for GG, GA, and AA in males, respectively. Besides, the mentioned genotype frequencies for females were 50%, 40.5%, and 9.5%, respectively. Moreover, there was a statistically significant correlation between VKORC1 gene −1639 G > A variant and warfarin maintenance dose (P < 0.001) but not for CYP2C9 variants. The results of the current study confirmed that the mutant variants of CYP2C9 are not frequent and do not have any impact on warfarin dose. In the case of VKORC1, the mutant allele (A) showed a positive correlation with warfarin dose adjustment. K E Y W O R D S CYP2C9, CYP450, dosage, polymorphisms, VKORC, warfarin How to cite this article: Fereidouni M, Moossavi M, Kazemi T, Nouranihassankiade S, Asghari A. Association between polymorphisms of VKORC1 and CYP2C9 genes with warfarin maintenance dose in a group of warfarin users in Birjand city, Iran. J Cell Biochem. 2019;120:9588-9593.

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Influence of VKORC1 and CYP2C9 Polymorphisms on Daily Acenocoumarol Dose Requirement in South Indian Patients With Mechanical Heart Valves

Abstract: Presence of a mutant allele of VKORC1 (-1639A & 1173T) and CYP2C9 genes increased the odds of requiring a lower mean dosage of acenocoumarol. Studying the combination of genotypes in RHD patients could predict acenocoumarol dose requirement more accurately.

Cited by 11 publications

References 25 publications

VKORC1 and CYP2C9*3 Polymorphisms and Their Impacts to Acenocoumarol Dosage in Vietnamese Heart Valve Replacement Patients

VKORC1 and CYP2C9*3 Polymorphisms and Their Impacts to Acenocoumarol Dosage in Vietnamese Heart Valve Replacement Patients

Value of VKORC1 (−1639G>A) rs9923231 genotyping in predicting warfarin dose: A replication study in South Indian population

Association between polymorphisms of VKORC1 and CYP2C9 genes with warfarin maintenance dose in a group of warfarin users in Birjand city, Iran

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