Extended evidence for association between the melanoma inhibitory activity 3 gene and myocardial infarction

2011 ◽  
Vol 105 (04) ◽  
pp. 670-675 ◽  
Author(s):  
Anna Schatke ◽  
Hannah Wolferstetter ◽  
Jakob Mueller ◽  
Albert Schömig ◽  
Adnan Kastrati ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Inhibitory Activity ◽  
Chromosome 1 ◽  
Nucleotide Polymorphisms ◽  
Current Cigarette Smoking ◽  
A Genome ◽  
Increased Risk ◽  
Melanoma Inhibitory Activity ◽  
History Of ◽  
The Impact

SummaryIn a genome-wide scan, isolated single nucleotide polymorphisms (SNPs), including rs17465637, in the melanoma inhibitory activity 3 gene (MIA3) on chromosome 1 were identified to be associated with coronary artery disease and myocardial infarction (MI). Because the role of common variation at the MIA3 locus has not yet been investigated, the aim of this case-control study was to determine the impact of haplotype-tagging SNPs and haplotypes in the MIA3 region on the risk of MI. In a set of nine haplotype-tagging SNPs, rs17465637, but none of the other SNPs, was associated with MI. After adjustments were made for age, gender, history of arterial hypertension, history of hyper-cholesterolaemia, current cigarette smoking and diabetes mellitus, multiple logistic regression analyses showed an increased risk in the carriers of one or two C alleles [adjusted odds ratio (OR) 1.17, 95% confidence interval (CI) 1.04–1.32, and 1.37, 95% CI 1.08–1.74, respectively]. Nine common haplotypes (frequency >1%) were established across the MIA3 region. Two of the haplotypes were associated with an increased risk of MI: the frequent (48%) TGACCAAAG haplotype and the rare (2%) CGACCAAAG haplotype (adjusted OR 1.102, 95% CI 1.002–1.212, and 1.574, 95% CI 1.077–2.298, respectively). Showing association between rs17465637 and MI, this work was consistent with results from the original detection study and most prior replication studies addressing this issue. In addition to correspond with such isolated evidence of association with MI, the present study identified specific haplotypes capturing the risk-related variation in the entire MIA3 region.

scholarly journals Atrial fibrillation and clinical outcomes 1 to 3 years after myocardial infarction

Open Heart ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. e001726
Author(s):  
Anthony P Carnicelli ◽  
Ruth Owen ◽  
Stuart J Pocock ◽  
David B Brieger ◽  
Satoshi Yasuda ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Clinical Outcomes ◽  
Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Increased Risk ◽  
History Of ◽  
The Impact

ObjectiveAtrial fibrillation (AF) and myocardial infarction (MI) are commonly comorbid and associated with adverse outcomes. Little is known about the impact of AF on quality of life and outcomes post-MI. We compared characteristics, quality of life and clinical outcomes in stable patients post-MI with/without AF.Methods/resultsThe prospective, international, observational TIGRIS (long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease) registry included 8406 patients aged ≥50 years with ≥1 atherothrombotic risk factor who were 1–3 years post-MI. Patient characteristics were summarised by history of AF. Quality of life was assessed at baseline using EQ-5D. Clinical outcomes over 2 years of follow-up were compared. History of AF was present in 702/8277 (8.5%) registry patients and incident AF was diagnosed in 244/7575 (3.2%) over 2 years. Those with AF were older and had more comorbidities than those without AF. After multivariable adjustment, patients with AF had lower self-reported quality-of-life scores (EQ-5D UK-weighted index, visual analogue scale, usual activities and pain/discomfort) than those without AF. CHA2DS2-VASc score ≥2 was present in 686/702 (97.7%) patients with AF, although only 348/702 (49.6%) were on oral anticoagulants at enrolment. Patients with AF had higher rates of all-cause hospitalisation (adjusted rate ratio 1.25 [1.06–1.46], p=0.008) over 2 years than those without AF, but similar rates of mortality.ConclusionsIn stable patients post-MI, those with AF were commonly undertreated with oral anticoagulants, had poorer quality of life and had increased risk of clinical outcomes than those without AF.Trial registration numberClinicalTrials: NCT01866904.

scholarly journals MYLK and PTGS1 Genetic Variations Associated with Osteoporosis and Benign Breast Tumors in Korean Women

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 378
Author(s):  
Hye-Won Cho ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Genome Wide Association Study ◽  
Breast Tumors ◽  
Bone Fragility ◽  
Nucleotide Polymorphisms ◽  
Korean Women ◽  
Homozygous Genotype ◽  
A Genome ◽  
Increased Risk ◽  
The Impact ◽  
Benign Breast Tumors

Osteoporosis, characterized by reduced bone mass and increased bone fragility, is a disease prevalent in women. Likewise, breast cancer is a multifactorial disease and considered the major cause of mortality in premenopausal and postmenopausal women worldwide. Our data demonstrated the association of the MYLK gene and PTGS1 gene variants with osteoporosis and benign breast tumor risk and the impact of ovariectomy on osteoporosis in Korean women. We performed a genome-wide association study (GWAS) of women with osteoporosis and benign breast tumors. There were 60 single nucleotide polymorphisms (SNPs) and 12 SNPs in the MYLK and PTGS1 genes, associated with benign breast tumors and osteoporosis. Our study showed that women with homozygous MYLK rs12163585 major alleles had an increased risk of osteoporosis following ovariectomy compared to those with minor alleles. Women carrying the minor PTGS1 rs1213265 allele and not treated via ovariectomy carried a higher risk of osteoporosis than those who underwent ovariectomy with a homozygous genotype at the major alleles. Our results suggest that both the MYLK and PTGS1 genes are genetic factors associated with the phenotypes, and these associations appear to be modulated by ovariectomy.

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

scholarly journals An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Misbah Razzaq ◽  
Maria Jesus Iglesias ◽  
Manal Ibrahim-Kosta ◽  
Louisa Goumidi ◽  
Omar Soukarieh ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Biological Traits ◽  
Nucleotide Polymorphisms ◽  
Ann Model ◽  
Neural Network Approach ◽  
A Genome ◽  
Increased Risk ◽  
Artificial Neural

AbstractVenous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in ~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main findings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients. The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing sets, respectively. A GWAS on the LIME approximate identified a strong statistical association peak (rs1424597: p = 5.3 × 10–7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%, p = 0.005) and the EOVT (3% vs. 0%, p = 0.013) studies. In a sample of 112 COVID-19 patients known to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4 levels were associated (p = 0.025) with worsened respiratory function. Using an original integrated proteomics and genetics strategy, we identified PLXNA4 as a new susceptibility gene for PE whose exact role now needs to be further elucidated.

scholarly journals Past medical history of tumors other than meningioma is a negative prognostic factor for tumor recurrence in meningiomas WHO grade I

2021 ◽  
Author(s):  
Annamaria Biczok ◽  
Philipp Karschnia ◽  
Raffaela Vitalini ◽  
Markus Lenski ◽  
Tobias Greve ◽  
...  
Keyword(s):  
Medical History ◽  
Tumor Recurrence ◽  
Clinical History ◽  
Study Endpoint ◽  
Past Medical History ◽  
Who Grade ◽  
Increased Risk ◽  
History Of ◽  
Meningioma Recurrence ◽  
The Impact

Abstract Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.

scholarly journals Impact on hospital mortality and morbidity of right ventricular involvement among patients with acute left ventricular infarction

2006 ◽  
Vol 124 (4) ◽  
pp. 186-191 ◽  
Author(s):  
Afonso Celso Pereira ◽  
Roberto Alexandre Franken ◽  
Sandra Regina Schwarzwälder Sprovieri ◽  
Valdir Golin
Keyword(s):  
Myocardial Infarction ◽  
Hospital Mortality ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Hospital Death ◽  
Inferior Wall ◽  
Mortality And Morbidity ◽  
Killip Class ◽  
Increased Risk ◽  
The Impact

CONTEXT AND OBJECTIVE: There is uncertainty regarding the risk of major complications in patients with left ventricular (LV) infarction complicated by right ventricular (RV) involvement. The aim of this study was to evaluate the impact on hospital mortality and morbidity of right ventricular involvement among patients with acute left ventricular myocardial infarction. DESIGN AND SETTING: Prospective cohort study, at Emergency Care Unit of Hospital Central da Irmandade da Santa Casa de Misericórdia de São Paulo. METHODS: 183 patients with acute myocardial infarction participated in this study: 145 with LV infarction alone and 38 with both LV and RV infarction. The presence of complications and hospital death were compared between groups. RESULTS: 21% of the patients studied had LV + RV infarction. In this group, involvement of the dorsal and/or inferior wall was predominant on electrocardiogram (p < 0.0001). The frequencies of Killip class IV upon admission and 24 hours later were greater in the LV + RV group, along with electrical and hemodynamic complications, among others, and death. The probability of complications among the LV + RV patients was 9.7 times greater (odds ratio, OR = 9.7468; 95% confidence interval, CI: 2.8673 to 33.1325; p < 0.0001) and probability of death was 5.1 times greater (OR = 5.13; 95% CI: 2.2795 to 11.5510; p = 0.0001), in relation to patients with LV infarction alone. CONCLUSIONS: Patients with LV infarction with RV involvement present increased risk of early morbidity and mortality.

scholarly journals Call for Emergency Room Guidelines to Identify Hyperthyroid Patients Prior to Contrast Imaging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A922-A923
Author(s):  
Sandhya Bassin ◽  
Louis F Amorosa
Keyword(s):  
Atrial Fibrillation ◽  
Emergency Room ◽  
Definitive Treatment ◽  
Graves Disease ◽  
Contrast Imaging ◽  
Iodinated Contrast ◽  
Increased Risk ◽  
History Of ◽  
The Impact ◽  
Hyperthyroid Patients

Abstract Background: Thyrotoxicosis can be mistaken for conditions such as atrial fibrillation and pulmonary embolism (PE) given the nonspecific symptoms of fatigue, palpitations, and dyspnea. Patients often undergo further imaging on presentation to the emergency room (ER), many of which use iodine for contrast. This can put patients at increased risk for iodine induced hyperthyroidism and delay definitive treatment in patients with Graves’ disease, the most common cause of hyperthyroidism. Clinical Case: A 53-year-old male with history of hyperthyroidism, atrial fibrillation, and prior PE presented with palpitations to the ER. He developed worsening dyspnea on exertion and palpitations over the last three days. He was unable to afford his medications, including methimazole, for the last nine months. In the ER he was in atrial fibrillation with rapid ventricular response. Due to concern for PE, he underwent a CTA with contrast, which was negative. His physical exam was notable for a diffusely enlarged goiter. His labs showed low TSH &lt;0.01 (norm 0.35-5.50mIU/L) and high free T4 &gt;7.77 (norm 0.9-1.8ng/dL). TSH stimulating antibodies were elevated at 1.9 (norm &lt;1.3 TSI index), consistent with Graves’ hyperthyroidism. Endocrinology was then consulted for severe thyrotoxicosis, initially treating the patient with PTU and propranolol. The patient was transitioned to methimazole and continued propranolol on discharge. Since he was given contrast, plan was for repeat thyroid uptake scan and iodine ablation in 3 months. However, patient was not compliant with medications, resulting in readmission for thyrotoxicosis 3 months later. Conclusion: This case highlights the impact of increased use of contrast in imaging in hyperthyroid patients. Hyperthyroid patients are at an increased risk for emboli. However, iodine can cause contrast-induced hyperthyroidism and delay definitive treatment of Graves’ disease. As almost half of thyrotoxic patients receive iodinated contrast prior to an endocrine consultation, endocrinologists should work with emergency physicians to develop a set of guidelines to identify at risk populations for hyperthyroidism (1). We advocate for urgent thyroid testing in patients with new onset atrial fibrillation, a history of Graves’ disease, specific symptoms of Graves’, or those taking thyrotoxic-inducing medications. This will assist in determining if patients should receive a prophylactic dose of anti-thyroid medication prior to iodinated contrast imaging. These guidelines can help prevent contrast induced hyperthyroidism and disruptions in treatment of Graves’ while still imaging patients for other diagnoses on the differential. Reference: (1) Giacomini A, et al. Urgent thyroid-stimulating hormone testing in emergency medicine: A useful tool? J Emerg Med. 2015;49(4):481-487.

scholarly journals Genetic and pharmacological relationship between P-glycoprotein and increased cardiovascular risk associated with clarithromycin prescription: An epidemiological and genomic population-based cohort study in Scotland, UK

PLoS Medicine ◽  
2020 ◽  
Vol 17 (11) ◽  
pp. e1003372
Author(s):  
Ify R. Mordi ◽  
Benjamin K. Chan ◽  
N. David Yanez ◽  
Colin N. A. Palmer ◽  
Chim C. Lang ◽  
...  
Keyword(s):  
Cohort Study ◽  
Observational Cohort Study ◽  
Chronic Obstructive ◽  
Antibiotic Prescribing ◽  
Nucleotide Polymorphisms ◽  
Major Pathway ◽  
P Glycoprotein ◽  
Increased Risk ◽  
History Of ◽  
Observational Cohort

Background There are conflicting reports regarding the association of the macrolide antibiotic clarithromycin with cardiovascular (CV) events. A possible explanation may be that this risk is partly mediated through drug–drug interactions and only evident in at-risk populations. To the best of our knowledge, no studies have examined whether this association might be mediated via P-glycoprotein (P-gp), a major pathway for clarithromycin metabolism. The aim of this study was to examine CV risk following prescription of clarithromycin versus amoxicillin and in particular, the association with P-gp, a major pathway for clarithromycin metabolism. Methods and findings We conducted an observational cohort study of patients prescribed clarithromycin or amoxicillin in the community in Tayside, Scotland (population approximately 400,000) between 1 January 2004 and 31 December 2014 and a genomic observational cohort study evaluating genotyped patients from the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study, a longitudinal cohort study of 18,306 individuals with and without type 2 diabetes recruited between 1 December 1988 and 31 December 2015. Two single-nucleotide polymorphisms associated with P-gp activity were evaluated (rs1045642 and rs1128503 –AA genotype associated with lowest P-gp activity). The primary outcome for both analyses was CV hospitalization following prescription of clarithromycin versus amoxicillin at 0–14 days, 15–30 days, and 30 days to 1 year. In the observational cohort study, we calculated hazard ratios (HRs) adjusted for likelihood of receiving clarithromycin using inverse proportion of treatment weighting as a covariate, whereas in the pharmacogenomic study, HRs were adjusted for age, sex, history of myocardial infarction, and history of chronic obstructive pulmonary disease. The observational cohort study included 48,026 individuals with 205,227 discrete antibiotic prescribing episodes (34,074 clarithromycin, mean age 73 years, 42% male; 171,153 amoxicillin, mean age 74 years, 45% male). Clarithromycin use was significantly associated with increased risk of CV hospitalization compared with amoxicillin at both 0–14 days (HR 1.31; 95% CI 1.17–1.46, p < 0.001) and 30 days to 1 year (HR 1.13; 95% CI 1.06–1.19, p < 0.001), with the association at 0–14 days modified by use of P-gp inhibitors or substrates (interaction p-value: 0.029). In the pharmacogenomic study (13,544 individuals with 44,618 discrete prescribing episodes [37,497 amoxicillin, mean age 63 years, 56% male; 7,121 clarithromycin, mean age 66 years, 47% male]), when prescribed clarithromycin, individuals with genetically determined lower P-gp activity had a significantly increased risk of CV hospitalization at 30 days to 1 year compared with heterozygotes or those homozygous for the non-P-gp–lowering allele (rs1045642 AA: HR 1.39, 95% CI 1.20–1.60, p < 0.001, GG/GA: HR 0.99, 95% CI 0.89–1.10, p = 0.85, interaction p-value < 0.001 and rs1128503 AA 1.41, 95% CI 1.18–1.70, p < 0.001, GG/GA: HR 1.04, 95% CI 0.95–1.14, p = 0.43, interaction p-value < 0.001). The main limitation of our study is its observational nature, meaning that we are unable to definitively determine causality. Conclusions In this study, we observed that the increased risk of CV events with clarithromycin compared with amoxicillin was associated with an interaction with P-glycoprotein.

scholarly journals Donor genetic variants in interleukin-6 and interleukin-6 receptor associate with biopsy-proven rejection following kidney transplantation.

2021 ◽  
Author(s):  
Felix Poppelaars ◽  
Mariana Gaya da Costa ◽  
Siawosh K. Eskandari ◽  
Jeffrey Damman ◽  
Marc A. Seelen
Keyword(s):  
Kidney Transplantation ◽  
Renal Transplantation ◽  
Renal Transplant ◽  
Interleukin 6 ◽  
Medical Center ◽  
Organ Donors ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Major Player ◽  
The Impact

Rejection after kidney transplantation remains an important cause of allograft failure that markedly impacts morbidity. Cytokines are a major player in rejection, and we, therefore, explored the impact of interleukin-6 (IL6) and IL-6 receptor (IL6R) gene polymorphisms on the occurrence of rejection after renal transplantation. We performed an observational cohort study analyzing both donor and recipient DNA in 1,271 renal transplant-pairs from the University Medical Center Groningen in The Netherlands and associated single nucleotide polymorphisms (SNPs) with biopsy-proven rejection after kidney transplantation. The C-allele of the IL6R SNP (Asp358Ala: rs2228145 A>C, formerly rs8192284) in donor kidneys conferred a reduced risk of rejection following renal transplantation (HR 0.78 per C-allele; 95%-CI 0.67-0.90; P=0.001). On the other hand, the C-allele of the IL6 SNP (at position-174 in the promoter; rs1800795 G>C) in donor kidneys was associated with an increased risk of rejection for male organ donors (HR per C-allele 1.31; 95%-CI 1.08-1.58; P=0.0006), but not female organ donors (P=0.33). In contrast, neither the IL6 nor IL6R SNP in the recipient showed an association with renal transplant rejection. In conclusion, donor IL6 and IL6R genotypes but not recipient genotypes represent an independent prognostic marker for biopsy-proven renal allograft rejection.

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