Dataset Information

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

ABSTRACT: OBJECTIVE: To study the effects of ?-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region. METHODS: Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed. RESULTS: The rs2592551 polymorphism detection results were 136 cases of wild-type homozygous CC genotype (50.56%), 115 cases of heterozygous CT genotype (42.75%), 18 cases of homozygous TT genotype (6.69%). The allele frequency C was 71.93%, T was 28.07%. The stable warfarin dose average was 2.86?±?0.61 mg/d in patients with CC genotype, 3.59?±?0.93 mg/d in patients with CT genotype and 4.06?±?0.88 mg/d in patients with TT genotype. The warfarin dose in different genotypes were compared, there was statistically significant difference between CC and TT, CC and CT (P <0. 05), but the TT and CT showed no significant difference (P?>?0.05). CONCLUSION: In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in GGCX gene rs259251 loci required for significantly higher warfarin dose than those with CC genotype. Therefore, rs2592551 polymorphism may one of the factors affecting the warfarin dose in patients with atrial fibrillation.

SUBMITTER: Kamali X

PROVIDER: S-EPMC4015881 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Kamali Xiayizha X Wulasihan Muhuyati M Yang Yu-Chun YC Lu Wu-Hong WH Liu Zhi-Qiang ZQ He Peng-Yi PY

Lipids in health and disease 20131023

<h4>Objective</h4>To study the effects of γ-glutamyl carboxylase (GGCX) rs2592551 polymorphism on warfarin dose in atrial fibrillation patients in Xinjiang region.<h4>Methods</h4>Polymerase chain reaction - restriction fragment length polymorphism and direct sequencing methods were used to detect the rs2592551 genotype in 269 atrial fibrillation patients with warfarin administration. The effects of different genotypes on warfarin dose were statistically analyzed.<h4>Results</h4>The rs2592551 pol ...[more]

PMID: 24148610

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Project description:ImportanceBleeding and thrombotic events (eg, stroke and systemic embolism) are common in patients with atrial fibrillation (AF) taking warfarin sodium despite a well-established therapeutic range.ObjectiveTo evaluate whether history of therapeutic warfarin control in patients with AF is independently associated with subsequent bleeding or thrombotic events.Design, setting, and participantsIn this multicenter cohort study of 176 primary care, cardiology, and electrophysiology clinics in the United States, data were obtained during 51 830 visits among 10 137 patients with AF in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry; 5545 patients treated with warfarin were included in the bleeding analysis, and 5635 patients were included in the thrombotic event analysis. Patient follow-up was performed from June 29, 2010, to November 30, 2014. Data analysis was performed from August 4, 2016, to February 15, 2019.ExposuresMultiple measures of warfarin control within the preceding 6 months were analyzed: time in therapeutic range of 2.0 to 3.0, most recent international normalized ratio (INR), percentage of time that a patient had interpolated INR values less than 2.0 or greater than 3.0, INR variance, INR range, and percentage of INR values in therapeutic range.Main outcomes and measuresAssociation of INR measures, alone or in combination, with clinical factors and risk for thrombotic events and bleeding during the subsequent 6 months was assessed post hoc using logistic regression models.ResultsA total of 5545 patients (mean [SD] age, 74.5 [9.8] years; 3184 [57.4%] male) with AF were included in the major bleeding analysis and 5635 patients (mean [SD] age, 74.5 [9.8] years; 3236 [57.4%] male) in the thrombotic event analysis. During a median follow-up of 1.5 years (interquartile range, 1.0-2.5 years), there were 339 major bleeds (6.1%) and 51 strokes (0.9%). Multiple metrics of warfarin control were individually associated with subsequent bleeding. After adjustment for clinical bleeding risk, 3 measures-time in therapeutic range (per 1-SD increase ≤55: adjusted odds ratio [aOR], 1.16; 95% CI, 1.02-1.32), variation in INR values (aOR, 1.32; 95% CI, 1.19-1.47), and maximum INR (aOR, 1.20; 95% CI, 1.10-1.31)-remained associated with bleeding risk. Adding INR variance to a clinical risk model slightly increased the C statistic from 0.68 to 0.69 and had a net reclassification improvement index of 0.028 (95% CI, -0.029 to 0.067). No INR measures were associated with subsequent stroke risk.Conclusions and relevanceThree metrics of prior warfarin control were associated with bleeding risk but only marginally more so than traditional clinical factors. This study did not identify any measures of INR control that were significantly associated with stroke risk.

Project description:OBJECTIVE:To investigate the correlation between KCNA5 single nucleotide polymorphism (SNP) and idiopathic atrial fibrillation (IAF). METHODS:A case-control study was conducted, including 282 cases of IAF patients and 300 cases of age and sex-matched normal controls; gene sequencing method was used to detect the distribution of KCNA5 SNP (rs3741930 and rs1056468) in the two groups. The IAF patients were divided into two groups based on the different genotypes of rs1056468 and rs3741930; differences in clinical parameters between the two groups of patients were compared. RESULTS:For rs3741930, the CC, CT and TT genotype frequencies in the IAF group were 16.7%, 50.0%, and 33.3% respectively; C allele frequency in IAF group was 41.7%; in the normal control group, those were 10.0%, 49.3%, 40.7% and 34.7% respectively; CC genotype frequency and C allele frequency in IAF group were significantly higher compared with the control group (P=0.019, P=0.014). For rs1056468, the AA, AT and TT genotype frequencies in the IAF group were 44.3%, 48.6%, and 7.1% respectively; in 300 cases of normal controls, those were 38.7%, 50.7%, and 10.6% respectively; A allele frequency in IAF group was 68.6 %, and it was 64.0% in normal controls. There were no significant differences in genotype and allele frequencies between control and IAF groups (P>0.05). In IAF group, among different genotypes of rs1741930 and rs1056468, there were no significant differences in age, SBP, DBP, HR, LAD and LVEF (P>0.05). While the BMI in CC and CC+TT groups of rs3741930 locus were 26.9±2.3 Kg/m(2) and 24.8±2.5 Kg/m(2) respectively. There were statistical differences between the two groups (P=0.019). BMI in AA and AA+TT groups of rs1056468 locus were 24.9±2.7 Kg/m(2) and 26.4±2.4 Kg/m(2) respectively; There was statistically significant significance between the two groups (P=0.014). CONCLUSION:The single nucleotide polymorphism rs3741930 locus in KCNA5 gene was related to the risk of IAF; the population carrying C allele was more susceptible to IAF; the polymorphic loci, rs3741930 and rs1056468, were correlated with the BMI of IAF patients.

Project description:BackgroundThe relationship between the APOE gene polymorphism and lipid profiles and atrial fibrillation (AF) remains controversial. The current study purposed to investigate how the APOE gene SNPs (rs429358 and rs7412) and lipid profile are associated with the risk for AF among the Hakka population in southern China.MethodsFinally, 1367 patients were enrolled in this study, including 706 participants with AF (41 ~ 98 years old, 58.64 % male) and 661 non-AF subjects (28 ~ 95 years old, 59.46 % male). The collected data included baseline characteristics, medical history, laboratory tests and echocardiography parameters. A general linear model (two-way analysis of variance (ANOVA)) and Tukey post-hoc tests were applied to identify an APOE allele, AF group, and interaction effect on lipid profiles. Logistic regression analysis was performed to identify risk factors for AF.ResultsFor AF group, the most common genotype was E3/E3 (53.82 %), followed by E3/E4 (28.19 %), E2/E3 (13.60 %), E4/E4 (1.98 %), E2/E4 (1.84 %) and E2/E2 (0.57 %). The two-way ANOVA followed by the Tukey procedure showed the following: the lipid levels depended significantly on AF and APOE allele groups for TG, TC, LDL-C and Apo-B (all P < 0.001), and statistically significant interactions between AF and APOE allele were observed in the above 4 variables (all P < 0.05). Multivariate regression analysis indicated that age ≥ 65years (P < 0.001), high diastolic blood pressure (DBP ≥ 90mm Hg, P = 0.018), a high levels of total cholesterol (TC ≥ 5.2mmol/L, P < 0.001) and triglyceride (TG ≥ 1.7mmol/L, P = 0.028), but not the two SNPs of the APOE gene (rs7412 and rs429358) (OR 1.079, P = 0.683), were significant independent risk factors for AF in the study population.ConclusionsThe principal findings of this study showed that individuals at high risk for AF were those over 65 years of age, higher DBP as well as high levels of TC and TG among the southern China Hakka population. The levels of TG, TC, LDL-C and Apo-B depended significantly on AF and APOE allele groups, and statistically significant interactions between AF and APOE allele were observed in the above 4 variables, although the APOE gene SNPs (rs429358 and rs7412) were no significant risk for AF incidence. Further investigation is needed to elucidate whether other SNPs of the APOE gene have a bearing on AF incidents.

Dataset Information

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

Publications

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

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