Peroxisome Proliferator-Activated Receptor Pathway Gene Polymorphism Associated With Extent of Coronary Artery Disease in Patients With Type 2 Diabetes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial

Cresci, Sharon; Wu, Jun; Province, Michael A.; Spertus, John A.; Steffes, Michael W.; McGill, Janet B.; Alderman, Edwin L.; Brooks, Maria M.; Kelsey, Sheryl F.; Frye, Robert L.; Bach, Richard G.

doi:10.1161/circulationaha.111.029173

Cited by 28 publications

(17 citation statements)

References 43 publications

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“…We further assessed the issue of population stratification using a subgroup of 492 TRIUMPH subjects (382 Caucasian; 110 African American) who were genotyped as part of a separate project with a custom array containing 3,351 SNPs and 100 ancestry informative markers (27, 28). Using these SNPs, we estimated 10 principal components with Eigenstrat and repeated our analyses in this subgroup to assess whether population stratification impacted our findings.…”

Section: Methodsmentioning

confidence: 99%

Adrenergic-Pathway Gene Variants Influence Beta-Blocker–Related Outcomes After Acute Coronary Syndrome in a Race-Specific Manner

Cresci

Dorn

Jones

et al. 2012

Journal of the American College of Cardiology

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Objective Overcoming racial differences in acute coronary syndrome (ACS) outcomes is a strategic goal for US healthcare. Genetic polymorphisms in the adrenergic pathway appear to explain some outcome differences by race in other cardiovascular diseases treated with β-adrenergic receptor-blockade (BB). Whether these genetic variants are associated with survival among ACS patients treated with BB, and if this differs by race, is unknown. Background BB after ACS is a measure of quality care, but the effectiveness across racial groups, is less clear. Methods A prospective cohort of 2,673 ACS patients (2,072 Caucasian; 601 African Americans) discharged on BB from 22 U.S. hospitals were followed for 2 years. Subjects were genotyped for polymorphisms in ADRB1, ADRB2, ADRA2C, and GRK5. We used proportional hazards regression to model the effect of genotype on mortality, stratified by race and adjusted for baseline factors. Results The overall 2-year mortality rate was 7.5% for Caucasians and 16.7% for African Americans. The prognosis associated with different genotypes in these BB-treated patients differed by race. In Caucasians, ADRA2C 322-325 deletion (D) carriers had significantly lower mortality as compared with homozygous individuals lacking the deletion (HR 0.46; CI 0.21, 0.99; p=0.047; race-by-genotype interaction p= 0.053). In African Americans, the ADRB2 16R allele was associated with significantly increased mortality (HR for RG vs. GG =2.10; CI 1.14, 3.86; RR vs. GG =2.65; CI 1.38, 5.08; p=0.013; race-by-genotype interaction p=0.096). Conclusions Adrenergic pathway polymorphisms are associated with mortality in ACS patients receiving BB in a race-specific manner. Understanding the mechanism by which different genes impact post-ACS mortality differently in Caucasian and African Americans may illuminate opportunities to improve BB therapy in these groups.

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Section: Methodsmentioning

confidence: 99%

Adrenergic-Pathway Gene Variants Influence Beta-Blocker–Related Outcomes After Acute Coronary Syndrome in a Race-Specific Manner

Cresci

Dorn

Jones

et al. 2012

Journal of the American College of Cardiology

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“…We noted that the cancer concept was also closely related to that of genetics. We found here that the use of the keyword "pathway" highlighted all articles pertaining to cell signalling or gene pathways [20][21][22][23][24][25][26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Patient healthcare trajectory. An essential monitoring tool: a systematic review

Pinaire

Azé

Bringay

et al. 2017

Health Inf Sci Syst

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Background: Patient healthcare trajectory is a recent emergent topic in the literature, encompassing broad concepts. However, the rationale for studying patients' trajectories, and how this trajectory concept is defined remains a public health challenge. Our research was focused on patients' trajectories based on disease management and care, while also considering medico-economic aspects of the associated management. We illustrated this concept with an example: a myocardial infarction (MI) occurring in a patient's hospital trajectory of care. The patient follow-up was traced via the prospective payment system. We applied a semi-automatic text mining process to conduct a comprehensive review of patient healthcare trajectory studies. This review investigated how the concept of trajectory is defined, studied and what it achieves.Methods: We performed a PubMed search to identify reports that had been published in peer-reviewed journals between January 1, 2000 and October 31, 2015. Fourteen search questions were formulated to guide our review. A semi-automatic text mining process based on a semantic approach was performed to conduct a comprehensive review of patient healthcare trajectory studies. Text mining techniques were used to explore the corpus in a semantic perspective in order to answer non-a priori questions. Complementary review methods on a selected subset were used to answer a priori questions.Results: Among the 33,514 publications initially selected for analysis, only 70 relevant articles were semi-automatically extracted and thoroughly analysed. Oncology is particularly prevalent due to its already well-established processes of care. For the trajectory thema, 80% of articles were distributed in 11 clusters. These clusters contain distinct semantic information, for example health outcomes (29%), care process (26%) and administrative and financial aspects (16%). Conclusion:This literature review highlights the recent interest in the trajectory concept. The approach is also gradually being used to monitor trajectories of care for chronic diseases such as diabetes, organ failure or coronary artery and MI trajectory of care, to improve care and reduce costs. Patient trajectory is undoubtedly an essential approach to be further explored in order to improve healthcare monitoring.

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“…[2] Between April 11, 2005, and December 31, 2008, 4340 patients with AMI, from 24 U.S. hospitals were prospectively enrolled into the TRIUMPH observational cohort study, as previously described. [2, 10, 19] AMI patients were identified by an elevated troponin blood test and either diagnostic electrocardiogram (EKG) changes or ischemic symptoms. 2979 TRIUMPH patients consented to genetic testing.…”

Section: Methodsmentioning

confidence: 99%

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction

et al. 2018

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The CHRNA5 gene encodes a neurotransmitter receptor subunit involved in multiple processes, including cholinergic autonomic nerve activity and inflammation. Common variants in CHRNA5 have been linked with atherosclerotic cardiovascular disease. Association of variation in CHRNA5 and specific haplotypes with cardiovascular outcomes has not been described. The aim of this study was to examine the association of CHRNA5 haplotypes with gene expression and mortality among patients with acute myocardial infarction (AMI) and explore potential mechanisms of this association. Patients (N = 2054) hospitalized with AMI were genotyped for two common variants in CHRNA5. Proportional hazard models were used to estimate independent association of CHRNA5 haplotype with 1-year mortality. Both individual variants were associated with mortality (p = 0.0096 and 0.0004, respectively) and were in tight LD (D' = 0.99). One haplotype, HAP3, was associated with decreased mortality one year after AMI (adjusted HR = 0.42, 95% CI 0.26, 0.68; p = 0.0004). This association was validated in an independent cohort (N = 637) of post-MI patients (adjusted HR = 0.23, 95% CI 0.07, 0.79; p = 0.019). Differences in CHRNA5 expression by haplotype were investigated in human heart samples (n = 28). Compared with non-carriers, HAP3 carriers had threefold lower cardiac CHRNA5 mRNA expression (p = 0.023). Circulating levels of the inflammatory marker hsCRP were significantly lower in HAP3 carriers versus non-carriers (3.43 ± 4.2 versus 3.91 ± 5.1; p = 0.0379). Activation of the inflammasome, an important inflammatory complex involved in cardiovascular disease that is necessary for release of the pro-inflammatory cytokine IL-1 β, was assessed in bone marrow-derived macrophages (BMDM) from CHRNA5 knockout mice and wild-type controls. In BMDM from CHRNA5 knockout mice, IL-1β secretion was reduced by 50% compared to wild-type controls (p = 0.004). Therefore, a common haplotype of CHRNA5 that results in reduced cardiac expression of CHRNA5 and attenuated macrophage inflammasome activation is associated with lower mortality after AMI. These results implicate CHRNA5 and the cholinergic anti-inflammatory pathway in survival following AMI.

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Peroxisome Proliferator-Activated Receptor Pathway Gene Polymorphism Associated With Extent of Coronary Artery Disease in Patients With Type 2 Diabetes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes Trial

Cited by 28 publications

References 43 publications

Adrenergic-Pathway Gene Variants Influence Beta-Blocker–Related Outcomes After Acute Coronary Syndrome in a Race-Specific Manner

Adrenergic-Pathway Gene Variants Influence Beta-Blocker–Related Outcomes After Acute Coronary Syndrome in a Race-Specific Manner

Patient healthcare trajectory. An essential monitoring tool: a systematic review

A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction

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