Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang

Kamali, Xiayizha; Wulasihan, Muhuyati; Yang, Yuchun; Lü, Wei; Liu, Zhiqiang; He, Pengyi

doi:10.1186/1476-511x-12-149

Cited by 12 publications

(8 citation statements)

References 20 publications

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“…GGCX catalyzes the post-translational modification of vitamin K-dependent proteins, and is one of the candidate genes in individual differences of response to warfarin [ 28 ]. The polymorphism of rs699664 was associated with 4%–7% of the dosage difference.…”

Section: Discussionmentioning

confidence: 99%

Warfarin Dosage Response Related Pharmacogenetics in Chinese Population

Zou

Wang

et al. 2015

PLoS ONE

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ObjectivesAs the most frequently prescribed anticoagulant, warfarin has large inter-individual variability in dosage. Genetic polymorphisms could largely explain the differences in dosage requirement. rs9923231 (VKORC1), rs7294 (VKORC1), rs1057910 (CYP2C9), rs2108622 (CYP4F2), and rs699664 (GGCX) involved in the warfarin action mechanism and the circulatory vitamin K were selected to investigate their polymorphism characteristics and their effects on the pharmacodynamics and pharmacokinetics of warfarin in Chinese population.Methods220 patients with cardiac valve replacement were recruited. International normalized ratio and plasma warfarin concentrations were determined. The five genetic polymorphisms were genotyping by pyro-sequencing. The relationships of maintenance dose, plasma warfarin concentration and INR were assessed among groups categorized by genotypes.Resultsrs9923231 and rs7294 in VKORC1 had the analogous genotype frequencies (D’: 0.969). 158 of 220 recruited individuals had the target INR (1.5–2.5). Patients with AA of rs9923231 and CC of rs7294 required a significantly lower maintenance dose and plasma concentration than those with AG and TC, respectively. The mean weekly maintenance dose was also significantly lower in CYP2C9 rs1057910 mutated heterozygote than in patients with the wild homozygote. Eliminating the influence from environment factors (age, body weight and gender), rs9923231 and rs1057910 could explain about 32.0% of the variability in warfarin maintenance dose; rs7294 could explain 26.7% of the variability in plasma concentration. For patients with allele G of rs9923231 and allele T of rs7294, higher plasma concentration was needed to achieve the similar goal INR.ConclusionsA better understanding of the genetic variants in individuals can be the foundation of warfarin dosing algorithm and facilitate the reasonable and effective use of warfarin in Chinese.

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Section: Discussionmentioning

confidence: 99%

Warfarin Dosage Response Related Pharmacogenetics in Chinese Population

Zou

Wang

et al. 2015

PLoS ONE

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“…Studies in Caucasians and African-Americans show that CYP2C9 , [5] VKORC1 , [6–8] CYP4F2 , [9] EPHX1 , [10] CALU , [11] APOE , [12,13] and PROC [14] polymorphisms can significantly affect interindividual variability of warfarin dosing. In addition, several studies in Asian populations have found that polymorphisms in GGCX , [15,16] NQO1 , [17] and HNF4α [18] are also associated with warfarin dosing, indicating that gene polymorphisms affecting warfarin dose requirements vary among different racial groups. The genetic makeup of the Chinese population differs from that of other ethnic groups; therefore, novel gene loci influencing warfarin dosing were found in Chinese patients.…”

Section: Introductionmentioning

confidence: 99%

Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement

Cao

Zhang

et al. 2017

Medicine

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The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis. Multiple linear regression was performed by incorporating patients' clinical and genetic data to create a new algorithm for warfarin dosing. From the 96 SNPs analyzed, VKORC1 rs9923231, CYP1A2 rs2069514, CYP3A4 rs28371759, and APOE rs7412 were associated with higher average warfarin maintenance doses, whereas CYP2C9 rs1057910, EPHX1 rs2260863, and CYP4F2 rs2189784 were associated with lower warfarin doses (P < 0.05). Multiple linear regression analysis could estimate 44.4% of warfarin dose variability consisting of, in decreasing order, VKORC1 rs9923231 (14.2%), CYP2C9 * 3 (9.6%), body surface area (6.7%), CYP1A2 rs2069514 (3.7%), age (2.7%), CYP3A4 rs28371759 (2.5%), CYP4F2 rs2108622 (1.9%), APOE rs7412 (1.7%), and VKORC1 rs2884737 (1.4%). In the dosing algorithm we developed, we confirmed the strongest effects of VKORC1, CYP2C9 on warfarin dosing. In the limited sample set, we also found that novel genetic predictors (CYP1A2, CYP3A4, APOE, EPHX1, CYP4F2, and VKORC1 rs2884737) may be associated with warfarin dosing. Further validation is needed to assess our results in larger independent northern Chinese samples.Abbreviations: ANOVA = one-way analysis of variance, BMI = body mass index, BSA = body surface area, INR = international normalized ratio, IWPC = International Warfarin Pharmacogenetics Consortium, MHVR = mechanical heart valve replacement, SNP = single nucleotide polymorphism.

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“…. 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.…”

Section: Genes Primer Primer Sequencesmentioning

confidence: 94%

Gene Polymorphisms Associated with Atrial Fibrillation

Alkanlı¹,

Ay²,

Alkanli³

2018

Cardiac Arrhythmias

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Atrial fibrillation (AF), which causes severe health problems, is a multi-factor disorder and is increasing day by day. AF is known to be one of the most common cardiac arrhythmias in clinical practice. AF can also be described as a cardiac dysrhythmia that causes severe cardiovascular morbidity and mortality. AF is known as an independent risk factor for death and it occurs a significant risk of morbidity due to stroke. There are many diseases that contribute to the development of AF. Diseases such as aging, heart failure, heart valve disorders, myocardial infarction, hypertension and diabetes mellitus are important factors in the development of structural AF. It is a known fact that AF prevalence increases with age. The mechanism underlying of AF is not fully understood, but genetic factors play an important role in the pathogenesis of this disease. There have been many studies aimed at investigating the genetic basis of AF, especially in recent years. In these studies, many mutations and variants have emerged which are identified as genetic risk factors in the development of AF. Identification of gene polymorphisms that play a role in the development of AF will be an important guide in the development of new therapies for the treatment of this condition.

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Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang

Cited by 12 publications

References 20 publications

Warfarin Dosage Response Related Pharmacogenetics in Chinese Population

Warfarin Dosage Response Related Pharmacogenetics in Chinese Population

Clinical and genetic factors associated with warfarin maintenance dose in northern Chinese patients with mechanical heart valve replacement

Gene Polymorphisms Associated with Atrial Fibrillation

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