Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø Study

Sejrup, Joakim Knutsen; Morelli, Vânia M.; Løchen, Maja-Lisa; Njølstad, Inger; Mathiesen, Ellisiv B.; Wilsgaard, Tom; Hansen, John‐Bjarne; Brækkan, Sigrid Kufaas

doi:10.1002/rth2.12306

Cited by 8 publications

(10 citation statements)

References 38 publications

(75 reference statements)

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“…The presence of an interaction between rs2036914 (F11) and CAD increased the VTE risk among both the study populations who carried those risk factors. Sejrup et al found that myocardial infarction patients with ≥1 risk allele at rs2036914 (F11) had a 1.8-fold higher risk of PE ( 73 ). Furthermore, the risk of VTE was 1.5-fold higher among individuals with non-O blood type and myocardial infarction ( 73 ).…”

Section: Discussionmentioning

confidence: 99%

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The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions

Natae

Kósa

Sándor

et al. 2021

Front. Cardiovasc. Med.

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Background: Interactions between genetic and environmental risk factors (GxE) contribute to an increased risk of venous thromboembolism (VTE). Understanding how these factors interact provides insight for the early identification of at-risk groups within a population and creates an opportunity to apply appropriate preventive and curative measures.Objective: To estimate and compare GxE for VTE risk in the general Hungarian and Roma populations.Methods: The study was based on data extracted from a database consisting of results previously obtained from a complex health survey with three pillars (questionnaire-based, physical, and laboratory examinations) involving 406 general Hungarian and 395 Roma subjects. DNA was genotyped for rs121909567 (SERPINC1), rs1799963 (F2), rs2036914 (F11), rs2066865 (FGG), rs6025 (F5), and rs8176719 (ABO) polymorphisms. After allele frequency comparisons, the odds ratio (OR) was calculated for individual SNPs. Furthermore, genetic risk scores (weighted GRS, unweighted GRS) were computed to estimate the joint effect of the genetic factors. Multivariable linear regression analysis was applied to test the impact of GxE on VTE risk after interaction terms were created between genetic and VTE risk factors [diabetes mellitus (DM), cancer, chronic kidney diseases (CKD), coronary artery diseases (CAD), migraine, depression, obesity, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein (HDL-C), triglyceride (TG), and smoking].Results: Interestingly, the rs121909567 (SERPINC1, ATBp3 mutation) SNP was not present in the general population at all. However, the risk allele frequency was 1% among the Roma population, which might suggest a founder effect in this minority. This polymorphism multiplicatively interacted with CAD, CKD, cancer, DM, depression, migraine, and obesity. Even though interactions were not statistically significant, the trend of interaction showed the probability of an incremental VTE risk among the Roma population. The risk of VTE was 4.7 times higher (p > 0.05) for Roma subjects who had ≥3 wGRS (median value) compared with individuals having lower wGRS values but lower for the general subjects (OR = 3.1 × 10−8). Additionally, the risk of VTE was 6.6 times higher in the Roma population that had ≥3 risk alleles (median value) than in individuals with the 0–1 risk allele, and the overall risk was much higher for the Roma population (OR = 6.6; p > 0.05) than for the general Hungarian population (OR = 1.5; p > 0.05). Five positive and significant GxE interactions were identified in the Roma population. The risk of VTE was higher among depressive Roma subjects who carried the risk variant rs2036914 (β = 0.819, p = 0.02); however, this interaction was not significant for the general subjects. The joint presence of high levels of LDL-C and rs2066865 (FGG) increased the VTE risk only among Roma individuals (β = 0.389, p = 0.002). The possibility of VTE risk increment, as a result of a multiplicative interaction between rs8176719 (ABO) and cancer, was identified, which was higher for the Roma population (β = 0.370, p < 0.001) than for the general population (β = −0.042, p = 0.6). The VTE risk increased in the Roma population (β = 0.280, p = 0.001), but was higher in the general population (β = 0.423, p = 0.001) as a result of the multiplicative interaction between CAD and rs2036914 (F11). The presence of a multiplicative interaction between rs2066865 (FGG) and CAD increased the VTE risk for the Roma population (β = 0.143, p = 0.046) but not for the general population (β = −0.329, p < 0.001).Conclusions: rs121909567 (SERPINC1, ATBp3) was confirmed as a founder mutation in the Roma population. Our study revealed some evidence on the burden of the joint presence of genetic and environmental risk factors on VTE, although the finding is highly subjected to the selection and observational biases due to the very small number of VTE cases and the observational nature of the study design, respectively. As a result of higher genetic load and GxE interactions, this minority Roma population is at higher risk of VTE than the general Hungarian population. Thus, our results suggest the need for an intensive search for the rs121909567 (SERPINC1; ATBp3) founder mutation, which might be an important factor for the assessment of thrombotic disease susceptibility among the Roma population. In addition, we strongly recommend further studies among a large number of VTE cases to explore the more precise impact of genetic and environmental risk factors on VTE in the study populations.

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Section: Discussionmentioning

confidence: 99%

“…Sejrup et al found that myocardial infarction patients with ≥1 risk allele at rs2036914 (F11) had a 1.8-fold higher risk of PE ( 73 ). Furthermore, the risk of VTE was 1.5-fold higher among individuals with non-O blood type and myocardial infarction ( 73 ). Our finding was also consistent with this study.…”

Section: Discussionmentioning

confidence: 99%

The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions

Natae

Kósa

Sándor

et al. 2021

Front. Cardiovasc. Med.

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“…The intragenic rs505922 SNP has been shown to be responsible for differential ABO protein levels with an increasing effect for allele "C" and diminishing levels for allele "T" 27,28 . rs505922 is in LD with the O blood group SNP rs8176719, which has been repeatedly associated with an increased risk of venous thromboembolism [29][30][31][32] . The rs8176719 polymorphism has been also associated to Factor VIII levels 33 , malaria 34,35 , venous thromboembolism 36 , vWF levels 33 .…”

Section: Namementioning

confidence: 99%

Country-Level Factors Dynamics and ABO/Rh Blood Groups Contribution To COVID-19 Mortality

Monaco

Pantaleo²,

Amoroso

et al. 2021

Preprint

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Identifying factors related to COVID-19 mortality is important to deploy effective containment measures and to safeguard categories at risk. In the last months, several investigations have tried to ascertain essential features for predicting the COVID-19 mortality tolls depending on country-specific dynamics and population structure. Most studies focused on the initial outbreak of COVID-19 spanning the first half of 2020. Several variables, including obesity, health system indicators such as hospital bed density, and bacillus Calmette-Guerin vaccination have been reported as significantly associated to COVID-19 mortality. Here, we examined in different pandemic stages some of the mentioned associations as well as ABO and Rh blood group indicators, which have also been previously linked to COVID-19 severity and fatal outcome. Using a machine learning approach, we found that the “B+” blood group frequency is an important factor at all stages of the pandemic.

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“…Epidemiológiai adatokkal egybehangzó eredményeink [14] nem hoznak új információt a kor és nem tekintetében. [15] [16].…”

Section: Megbeszélésunclassified

The morphological response of the heart and spleen following acute myocardial infarction-induced sterile inflammation: a clinicopathological study

Iuliu

Nándor

Horváth

2019

Bulletin of Medical Sciences

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Introduction: as an outcome of sterile inflammation-inducing acute ischemic processes, many splenic cells enter the circulatory system and migrate into the lesion, defending tissues against the spread of ischemia or enhancing necrosis.Objective: investigating the therapeutic effect of splenic morphological response to sterile inflammation-inducing myocardial infarction.Material and method: We examined the weight and structure of the heart and spleen of 106 patients deceased due to acute myocardial infarction. These data were correlated with demographic (personal) and epidemiological data, and disease history. After morphological investigation of archived myocardial and splenic tissue samples, the acute ischemia-induced structural alterations of splenic samples were quantified using a digital morpho-metric method. Results were evaluated in comparison to the myocardial ischemia coefficient. Changes in distribution of ischemia-induced cell types were characterized by defining the immunological phenotypes of macrophages (M1 vs. M2). Spleen samples from patients without history of ischemia were used as controls.Results: The modification of the spleen weight was associated with an increase in peripheral blood leucocyte levels. Our morphological analysis proved a positive correlation between the ischemia coefficient and the decrease of spleen weight. Structural analysis of splenic tissue revealed the collapse of red pulp sinusoids, a significant size decrease of the white pulp marginal zone (p<0.05), and depleted follicles with irregular margins without any distinct germinative centers. Concurrently, with the proliferation of granulocytes, the increase of M1 macrophages was observed in the myocardium, and a higher M1/M2 ratio was detected in the marginal zone of splenic follicles.Conclusion: On the background of acute ischemia, time critically determines the dynamic structural changes of the spleen. Along with reducing the marginal zone, immunomodulation targeting its cellular composition will be a putative therapeutic approach in the future.

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Myocardial infarction, prothrombotic genotypes, and venous thrombosis risk: The Tromsø Study

Cited by 8 publications

References 38 publications

The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions

The Higher Prevalence of Venous Thromboembolism in the Hungarian Roma Population Could Be Due to Elevated Genetic Risk and Stronger Gene-Environmental Interactions

Country-Level Factors Dynamics and ABO/Rh Blood Groups Contribution To COVID-19 Mortality

The morphological response of the heart and spleen following acute myocardial infarction-induced sterile inflammation: a clinicopathological study

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