Dataset Information

Impact of polymorphisms of the GGCX gene on maintenance warfarin dose in Chinese populations: Systematic review and meta-analysis.

ABSTRACT: The meta-analysis was conducted to investigate the impact of gamma-glutamyl carboxylase (GGCX) on maintenance warfarin dose. 8 studies were included, focusing on the impact of GGCX single nucleotide polymorphisms (SNPs) on mean daily warfarin dose (MDWD). GGCX (rs699664; AA versus GG, GA versus GG, A versus GG) and GGCX (rs12714145; GA versus GG, AA versus GG, A versus GG) showed no significant differences on mean daily warfarin dose (MDWD). This meta-analysis was the first to report the relationship between GGCX SNPs and MDWD in Chinese populations. No evidence could be found in the relationship between SNPs of GGCX (rs699664 and rs12714145) and maintenance warfarin dose.

SUBMITTER: Tian L

PROVIDER: S-EPMC4473094 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Impact of polymorphisms of the GGCX gene on maintenance warfarin dose in Chinese populations: Systematic review and meta-analysis.

Tian Lihong L Zhang Jinhua J Xiao Shiji S Huang Jinlong J Zhang Yuanyuan Y Shen Jianzhen J

Meta gene 20150605

The meta-analysis was conducted to investigate the impact of gamma-glutamyl carboxylase (GGCX) on maintenance warfarin dose. 8 studies were included, focusing on the impact of GGCX single nucleotide polymorphisms (SNPs) on mean daily warfarin dose (MDWD). GGCX (rs699664; AA versus GG, GA versus GG, A versus GG) and GGCX (rs12714145; GA versus GG, AA versus GG, A versus GG) showed no significant differences on mean daily warfarin dose (MDWD). This meta-analysis was the first to report the relatio ...[more]

PMID: 26106580

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Project description:BackgroundWarfarin is the most recommended oral anticoagulant after artificial mechanical valve replacement therapy. However, the narrow therapeutic window and varying safety and efficacy in individuals make dose determination difficult. It may cause adverse events such as hemorrhage or thromboembolism. Therefore, advanced algorithms are urgently required for the use of warfarin.ObjectiveTo establish a warfarin dose model for patients after prosthetic mechanical valve replacement in southern China in combination with clinical and genetic variables, and to improve the accuracy and ideal prediction percentage of the model.MethodsClinical data of 476 patients were tracked and recorded in detail. The gene polymorphisms of VKORC1 (rs9923231, rs9934438, rs7196161, and rs7294), CYP2C9 (rs1057910), CYP1A2 (rs2069514), GGCX (rs699664), and UGT1A1 (rs887829) were determined using Sanger sequencing. Multiple linear regressions were used to analyze the gene polymorphisms and the contribution of clinical data variables; the variables that caused multicollinearity were screened stepwise and excluded to establish an algorithm model for predicting the daily maintenance dose of warfarin. The ideal predicted percentage was used to test clinical effectiveness.ResultsA total of 395 patients were included. Univariate linear regression analysis suggested that CYP1A2 (rs2069514) and UGT1A1 (rs887829) were not associated with the daily maintenance dose of warfarin. The new algorithm model established based on multiple linear regression was as follows: Y = 1.081 - 0.011 (age) + 1.532 (body surface area)-0.807 (rs9923231 AA) + 1.788 (rs9923231 GG) + 0.530 (rs1057910 AA)-1.061 (rs1057910 AG)-0.321 (rs699664 AA). The model accounted for 61.7% of individualized medication differences, with an ideal prediction percentage of 69%.ConclusionGGCX (rs699664) may be a potential predictor of warfarin dose, and our newly established model is expected to guide the individualized use of warfarin in clinical practice in southern China.

Project description:BackgroundApolipoprotein E (apoE) induces the uptake of vitamin K-rich lipoproteins by the liver, which likely affects inter-individual variation of warfarin dosing requirements. Associations between APOE polymorphisms and warfarin dosing were previously reported inconsistently among different ethnic groups, so the present study investigated this association in northern Han Chinese patients with mechanical heart valve prosthesis.MethodsA total of 186 patients who underwent mechanical heart valve replacement and attained a stable warfarin dose were included. APOE single nucleotide polymorphisms (SNPs) rs7412 and rs429358 were genotyped using Illumina SNP GoldenGate Assay. Genotyping results were confirmed by direct sequencing. PHASE v2.1 software was used to construct rs7412 and rs429358 haplotypes. The effects of different APOE genotypes on warfarin dose were analyzed statistically.ResultsThe mean warfarin maintenance dose was 3.10 ± 0.96 mg/day, and the mean international normalized ratio (INR) was 2.09 ± 0.24. APOE E2, E3, and E4 allele frequencies were 11.6 %, 82.5 %, and 5.9 %, respectively. No E2/E2 or E4/E4 genotypes were detected in this population. E2/E3, E3/E3, E2/E4, and E3/E4 genotype frequencies were 21.0 %, 67.2 %, 2.2 %, and 9.7 %, respectively. Significant differences in warfarin dose requirements were observed among patients with E2/E3, E3/E3, and E3/E4 genotypes (p < 0.05). In post hoc comparison, daily warfarin maintenance doses were significantly higher in E2/E3 heterozygotes compared with E3/E3 homozygotes (p < 0.05), but no differences in dose requirements were found between E3/E4 and E3/E3, or E2/E3 and E3/E4 (p > 0.05). Patients were divided into low-intensity anticoagulant treatment group (1.6 ≤ INR <2.0) and relatively high-intensity anticoagulant treatment group (2.0 ≤ INR ≤ 2.5), and significantly higher warfarin dose requirements were observed in E2/E3 heterozygotes compared with E3/E3 homozygotes in both subgroups (p < 0.05). Multivariable analysis adjusting for other confounders showed that E2/E3 genotype was associated with a significantly higher warfarin dose compared with E3/E3 genotype (p < 0.05).ConclusionsAPOE allele and genotype frequencies in the northern Han Chinese population appear to differ from other racial groups or populations living in other regions of China. The APOE E2 variant was associated with a significantly higher warfarin maintenance dose. Thus, APOE polymorphisms could be one of the predictors influencing warfarin doses in this population.

Dataset Information

Impact of polymorphisms of the GGCX gene on maintenance warfarin dose in Chinese populations: Systematic review and meta-analysis.

Publications

Impact of polymorphisms of the GGCX gene on maintenance warfarin dose in Chinese populations: Systematic review and meta-analysis.

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