Dataset Information

Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation.

ABSTRACT: Genetic risk score (GRS) analysis is a popular approach to derive individual risk prediction models for complex diseases. In venous thrombosis (VT), such type of analysis shall integrate information at the ABO blood group locus, which is one of the major susceptibility loci. However, there is no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when properly assessing association between ABO locus and VT risk. Using comprehensive haplotype analyses of ABO blood group tagging SNPs in 5425 cases and 8445 controls from 6 studies, we demonstrate that using only rs8176719 (tagging O1) to correctly assess the impact of ABO locus on VT risk is suboptimal, because 5% of rs8176719-delG carriers do not have an increased risk of developing VT. Instead, we recommend the use of 4 SNPs, rs2519093 (tagging A1), rs1053878 (A2), rs8176743 (B), and rs41302905 (O2), when assessing the impact of ABO locus on VT risk to avoid any risk misestimation. Compared with the O1 haplotype, the A2 haplotype is associated with a modest increase in VT risk (odds ratio, ∼1.2), the A1 and B haplotypes are associated with an ∼1.8-fold increased risk, whereas the O2 haplotype tends to be slightly protective (odds ratio, ∼0.80). In addition, although the A1 and B blood groups are associated with increased von Willebrand factor and factor VIII plasma levels, only the A1 blood group is associated with ICAM levels, but in an opposite direction, leaving additional avenues to be explored to fully understand the spectrum of biological effects mediated by ABO locus on cardiovascular traits.

SUBMITTER: Goumidi L

PROVIDER: S-EPMC8085481 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation.

Goumidi Louisa L Thibord Florian F Wiggins Kerri L KL Li-Gao Ruifang R Brown Mickael R MR van Hylckama Vlieg Astrid A Souto Joan-Carles JC Soria José-Manuel JM Ibrahim-Kosta Manal M Saut Noémie N Daian Delphine D Olaso Robert R Amouyel Philippe P Debette Stéphanie S Boland Anne A Bailly Pascal P Morrison Alanna C AC Mook-Kanamori Denis O DO Deleuze Jean-François JF Johnson Andrew A de Vries Paul S PS Sabater-Lleal Maria M Chiaroni Jacques J Smith Nicholas L NL Rosendaal Frits R FR Chasman Daniel I DI Trégouët David-Alexandre DA Morange Pierre-Emmanuel PE

Blood 20210401 17

Genetic risk score (GRS) analysis is a popular approach to derive individual risk prediction models for complex diseases. In venous thrombosis (VT), such type of analysis shall integrate information at the ABO blood group locus, which is one of the major susceptibility loci. However, there is no consensus about which single nucleotide polymorphisms (SNPs) must be investigated when properly assessing association between ABO locus and VT risk. Using comprehensive haplotype analyses of ABO blood gr ...[more]

PMID: 33512453

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Project description:Gamma-glutamyl transferase (GGT) is a biomarker of inflammation, and is known to be associated with stroke and atrial fibrillation. Venous thromboembolism (VT), a not uncommon thrombotic disorder, shares similar mechanisms with other thrombotic disorders including these stroke and atrial fibrillation. Given these associations, we intended to investigate the potential association between variability in GGT and VT. The study included data from the National Health Insurance Service-Health Screening Cohort, comprising 1,085,105 participants with health examinations 3 or more times from 2003 to 2008. Variability indexes were the coefficient of variation, standard deviation, and variability independent of the mean. The occurrence of venous thromboembolism (VT) was defined with more than one claim of the following ICD-10 codes: deep VT (I80.2-80.3), pulmonary thromboembolism (I26), intraabdominal venous thrombosis (I81, I82.2, I82.3), or other VT (I82.8, I82.9). To determine the relationship of quartiles of GGT with incident VT risk, Kaplan-Meier survival curve and logrank test were used. Cox's proportional hazard regression was used to investigate the risk of VT occurrence by GGT quartile (Q1-Q4). A total of 1,085,105 subjects were incorporated in the analysis, and the average follow-up was 12.4 years (interquartile range 12.2-12.6). VT occurred in 11,769 (1.08%) patients. The GGT level was measured 5,707,768 times in this stud. Multivariable analysis showed that GGT variability were positively associated with the occurrence of VT. Compared to the Q1, the Q4 showed an adjusted HR of 1.15 (95% CI 1.09-1.21, p < 0.001) when using coefficient of variation, 1.24 (95% CI 1.17-1.31, p < 0.001) when using standard deviation, and 1.10 (95% CI 1.05-1.16, p < 0.001) when using variability independent of the mean. Increased variability of GGT may be related to an increased risk of VT. Maintaining a stable GGT level would be beneficial in reducing the risk of VT.

Project description:UnlabelledEssentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous ThromboembolismSummaryBackground Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT.

Project description:BackgroundThis meta-analysis evaluated the association of ABO blood type on central venous catheter-related thrombosis (CRT).MethodsData were derived from 8477 patients at Sichuan Cancer Hospital from January 2015 to December 2021 and articles previously published in Chinese and English databases. Data from our hospital were collected by reviewing electronic medical records. Searched databases included CNKI, VIP, Wan Fang, China Biomedical, PubMed, Cochrane Library, Web of Science, EMBASE, CINAHL, and OVID (up to July 2023). All statistical analyses were performed using SPSS 22.0 and Revman 5.3. The Bonferroni method was used to adjust the α test level for reducing the risk of I errors in the multiple comparisons. A P-value < 0.05 was considered statistically significant. Continuous variables were analyzed using a two-independent sample T test. The chi-squared test was used to analyze categorical data.ResultsA total of 818 studies were identified in the search. However, only four studies met the inclusion criteria. Combined with data from our hospital, five studies were included with a total of 18407 cases. Those studies only focused on peripherally inserted central catheter (PICC). According to the data from our hospital, logistic regression revealed that myelosuppression [odds ratio (OR), 1.473; P = 0.005) and radiotherapy(OR, 1.524; P<0.001) were independent risk factors for symptomatic PICC- VTE. Blood types A (OR, 1.404; P = 0.008), B (OR, 1.393; P = 0.016), and AB (OR, 1.861; P<0.001) were associated with a significantly higher risk of symptomatic PICC-VTE than blood type O. And the hematologic tumor has a significantly higher risk of PICC-VTE than breast cancer (OR, 0.149; P < 0.001), and gynecological tumor (OR, 0.386; P = 0.002). In the meta-analysis of the association between ABO blood type and PICC related thrombosis, the I2 statistic was not significant in any of the pairwise comparisons, and a fixed-effects model was subsequently used for all analyses. The meta-analysis indicated that the incidence of symptomatic PICC related thrombosis was significantly lower in individuals with the O blood type (3.30%) than in those with the A (4.92%), B (5.20%), or AB (6.58%) blood types (all P < 0.0083). However, in the pairwise comparisons among A, B, and AB, the differences were nonsignificant (P > 0.0083).ConclusionsAccording to the results from our single center analysis, we found that myelosuppression, radiotherapy, hematologic tumor, and non-O blood type were independent risk factors for symptomatic PICC related thrombosis. In the meta-analysis of further exploration of ABO blood type and PICC related thrombosis, we found that ABO blood type may influence PICC related thrombosis, and individuals with the O blood type had a lower risk of PICC related thrombosis than those with non-O blood type.

Project description:In studies of time-to-events, it is common to collect information about events that occurred before the inclusion in a prospective cohort. When the studied risk factors are independent of time, including both pre- and post-inclusion events in the analyses, generally referred to as relying on an ambispective design, increases the statistical power but may lead to a selection bias. In the field of venous thromboembolism (VT), ABO blood groups have been the subject of extensive research due to their substantial effect on VT risk. However, few studies have investigated their effect on the risk of VT recurrence. Motivated by the study of the association of genetically determined ABO blood groups with VT recurrence, we propose a methodology to include pre-inclusion events in the analysis of ambispective studies while avoiding the selection bias due to mortality. This work relies on two independent cohorts of VT patients, the French MARTHA study built on an ambispective design and the Dutch MEGA study built on a standard prospective design. For the analysis of the MARTHA study, a weighted Cox model was developed where weights were defined by the inverse of the survival probability at the time of data collection about the events. Thanks to the collection of information on the vital status of patients, we could estimate the survival probabilities using a delayed-entry Cox model on the death risk. Finally, results obtained in both studies were then meta-analysed. In the combined sample totalling 2,752 patients including 993 recurrences, the A1 blood group has an increased risk (Hazard Ratio (HR) of 1.18, p = 4.2 × 10-3) compared with the O1 group, homogeneously in MARTHA and in MEGA. The same trend (HR = 1.19, p = 0.06) was observed for the less frequent A2 group. The proposed methodology increases the power of studies relying on an ambispective design which is frequent in epidemiologic studies about recurrent events. This approach allowed to clarify the association of ABO blood groups with the risk of VT recurrence. Besides, this methodology has an immediate field of application in the context of genome wide association studies.

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Dataset Information

Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation.

Publications

Association between ABO haplotypes and the risk of venous thrombosis: impact on disease risk estimation.

Similar Datasets

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