scholarly journals Interferon Regulatory Factor 5 (IRF5) Gene Haplotypes Are Associated with Premature Coronary Artery Disease Association of the IRF5 Polymorphisms with Cardiometabolic Parameters the Genetics of Atherosclerotic Disease (GEA) Mexican Study

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 443
Author(s):  
Rosalinda Posadas-Sánchez ◽  
Guillermo Cardoso-Saldaña ◽  
José Manuel Fragoso ◽  
Gilberto Vargas-Alarcón

Interferon regulatory factor 5 (IRF5) has an important role in the inflammatory process, a fundamental component of coronary artery disease (CAD). Thus, the objective of this study was to evaluate the association of IRF5 polymorphisms with the development of premature CAD (pCAD) and cardiometabolic parameters. IRF5 polymorphisms (rs1874330, rs3778754, rs3757386, rs3757385, rs3807134, rs3807135, and rs6968563) were determined in 1116 pCAD patients and 1003 controls. Polymorphism distribution was similar in patients and controls; however, the haplotype analysis showed five haplotypes with a different distribution. TGCGTCT (OR (odds ratio) = 1.248, p = 0005) and TCTGCCT (OR = 10.73, p < 0.0001) were associated with a high risk, whereas TCCGTCT (OR = 0.155, p < 0.0001), CGCTTTT (OR = 0.108, p < 0.0001), and TCCGCCT (OR = 0.014, p < 0.0001) were associated with a low risk of pCAD. Associations with aspartate aminotransferase, hypertriglyceridemia, magnesium deficiency, triglycerides/HDL-C index, LDL-C, and adiponectin levels were observed in pCAD patients. In controls, associations with hypoalphalipoproteinemia, non-HDL-C, apolipoprotein B, hyperuricemia, TNF-α, IL-6, IL-15, valvular calcification, and subclinical hypothyroidism were observed. In summary, five haplotypes were associated with pCAD, two with high risk and three with low risk. Some IRF5 polymorphisms were associated with cardiometabolic parameters in pCAD patients and control.

2021 ◽  
Vol 12 ◽  
pp. 204062232110243
Author(s):  
Jingwen Yong ◽  
Jinfan Tian ◽  
Xin Zhao ◽  
Xueyao Yang ◽  
Haoran Xing ◽  
...  

Background: Coronary artery disease (CAD) is the leading cause of death in advanced kidney disease. However, its best treatment has not been determined. Methods: We searched PubMed and Cochrane databases and scanned references to related articles. Studies comparing the different treatments for patients with CAD and advanced CKD (estimated glomerular filtration rate <30 ml/min/1.73 m2 or dialysis) were selected. The primary result was all-cause death, classified according to the follow-up time: short-term (<1 month), medium-term (1 month-1 year), and long-term (>1 year). Results: A total of 32 studies were selected to enroll 84,498 patients with advanced kidney disease. Compared with medical therapy (MT) alone, percutaneous coronary intervention (PCI) was associated with low risk of short-, medium-term and long-term all-cause death (more than 3 years). For AMI patients, compared with MT, PCI was not associated with low risk of short- and medium-term all-cause death. For non-AMI patients, compared with MT, PCI was associated with low risk of long-term mortality (more than 3 years). Compared with MT, coronary artery bypass surgery (CABG) had no significant advantages in each follow-up period of all-cause death. Compared with PCI, CABG was associated with a high risk of short-term death, but low risk of long-term death: 1–3 years; more than 3 years. CABG could also reduce the risk of long-term risk of cardiac death, major adverse cardiovascular events (MACEs), myocardial infarction (MI), and repeat revascularization. Conclusions: In patients with advanced kidney disease and CAD, PCI reduced the risk of short-, medium- and long- term (more than 3 years) all-cause death compared with MT. Compared with PCI, CABG was associated with a high risk of short-term death and a low risk of long-term death and adverse events.


1994 ◽  
Vol 109 (1-2) ◽  
pp. 276-277
Author(s):  
H.W. Hahmann ◽  
S. Kohring ◽  
W. Steinbrecher ◽  
M. Bodis ◽  
D. Becker ◽  
...  

Author(s):  
Fernando Riveros-Mckay ◽  
Michael E. Weale ◽  
Rachel Moore ◽  
Saskia Selzam ◽  
Eva Krapohl ◽  
...  

AbstractBackgroundThere is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment.MethodsThis research has been conducted using the UK Biobank (UKB) resource. We developed our own polygenic risk score (PRS) for coronary artery disease (CAD), using novel and established methods to combine published genomewide association study (GWAS) data with data from 114,196 UK Biobank individuals, also leveraging a large resource of other GWAS datasets along with functional information, to aid in the identification of causal variants, and thence define weights for > 8M genetic variants. We utilised a further 60,000 UKB individuals to develop an integrated risk tool (IRT) that combined our PRS with established risk tools (either the American Heart Association/American College of Cardiology’s pooled cohort equations (PCE) or the UK’s QRISK3) which was then tested in an additional, independent, set of 212,563 UKB individuals. We evaluated prediction performance in individuals of European ancestry, both as a whole and stratified by age and sex.FindingsThe novel CAD PRS showed superior predictive power for CAD events, compared to other published PRSs. As an individual risk factor, it has similar predictive power to each of systolic blood pressure, HDL cholesterol, and LDL cholesterol, but is more predictive than total cholesterol and smoking history. Our novel CAD PRS is largely uncorrelated with PCE, QRISK3, and family history, and, when combined with PCE into an integrated risk tool, had superior predictive accuracy. In individuals reclassified as high risk, CAD event rates were markedly and significantly higher compared to those reclassified as low risk. Overall, 9.7% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, in contrast to 3.7% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.7% (95% CI 4.4−7.0), but when individuals were stratified into four age-by-sex subgroups the improvement was larger for all subgroups (range 7.7%−17.3%), with best performance in younger middle-aged men aged 40–54yo (17.3%, 95% CI 13.0–21.5). Broadly similar results were found using a different risk tool (QRISK3), and also for cardiovascular disease events defined more broadly.InterpretationAn integrated risk tool that includes polygenic risk outperforms current, clinical risk stratification tools, and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person’s polygenic risk.FundingGenomics plc


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Zhengxi Xu ◽  
Hanning Liu ◽  
Cheng Sun ◽  
Ke Si ◽  
Yan Zhao ◽  
...  

Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. Left main coronary artery disease (LMCAD) is a severe phenotype of CAD and has a genetic component. Previous studies identified 3 inflammation-related single nucleotide polymorphisms (SNPs) contributing to the development of LMCAD. We integrated these SNPs into a genetic risk score for the prediction of LMCAD. We enrolled 1544 patients with CAD between 2007 and 2011. The individual associations of the 3 SNPs with LMCAD were assessed. We then calculated the genetic risk score for each patient and stratified patients into low-risk, intermediate-risk, and high-risk categories of genetic risk. In univariable logistic regression analysis, the odds of LMCAD for the high-risk group were 2.81 (95% confidence interval [CI]: 1.72-4.60; P = 0.02) times those of the low-risk group. After adjustment for CAD-related clinical variables, the high-risk group (adjusted OR: 2.78; 95% CI: 1.69-4.58; P = 0.02) had increased odds of LMCAD when compared with the low-risk group. Comparison of model c-statistics showed greater predictive value with regard to LMCAD for the genetic risk score model than the models including single SNPs.


Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1018
Author(s):  
Fabiola López-Bautista ◽  
Rosalinda Posadas-Sánchez ◽  
Gilberto Vargas-Alarcón

Interleukin 37 (IL-37) is an anti-inflammatory cytokine expressed in foam cells located in the atherosclerosis plaques. The present study aimed to evaluate the association of the IL-37 polymorphisms with premature coronary artery disease (pCAD), cardiovascular risk factors, metabolic parameters, and levels of liver enzymes. Three IL-37 polymorphisms (rs6717710, rs2708961, and rs2708947) were determined in 1161 patients with pCAD and 951 healthy controls. IL-37 polymorphisms were not associated with the presence of pCAD. The association of the polymorphisms with cardiovascular risk factors, metabolic parameters, and levels of liver enzymes was evaluated independently in pCAD and healthy controls. In pCAD patients, under different models, the rs6717710 was associated with low risk of having elevated alkaline phosphatase (ALP) (padditive = 0.020; pdominant = 0.02; pheterozygous = 0.04; pcodominant1 = 0.040). On the other hand, in healthy controls, the rs6717710 was associated with low risk of having elevated levels of alanine aminotransferase (ALT) (padditive = 0.04, precessive = 0.01, pcodominant2 = 0.01) and aspartate aminotransferase (AST) (padditive = 0.02, pdominant = 0.02). The IL-37 polymorphisms were not associated with the risk of pCAD. In pCAD patients, the rs6717710 was associated with low risk of having elevated ALP levels, whereas in controls was associated with low risk of having elevated ALT and AST levels.


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