Influence of 9p21.3 Genetic Variants on Clinical and Angiographic Outcomes in Early-Onset Myocardial Infarction

Ardissino, Diego; Berzuini, Carlo; Merlini, Piera Angelica; Mannucci, Pier Mannuccio; Surti, Aarti; Burtt, Noél P.; Voight, Benjamin F.; Tubaro, Marco; Peyvandi, Flora; Spreafico, M.; Celli, Patrizia; Lina, Daniela; Notarangelo, Maria Francesca; Ferrario, Maurizio; Fetiveau, Raffaela; Casari, Giorgio; Galli, Michele; Ribichini, Flavio; Rossi, Marco; Bernardi, Francesco; Marziliano, Nicola; Zonzin, Pietro; Mauri, Francesco; Piazza, Alberto; Foco, Luisa; Bernardinelli, Luisa; Altshuler, David; Kathiresan, Sekar; Atherosclerosis, Thrombosis Italian; Investigators, Vascular Biology

doi:10.1016/j.jacc.2010.11.075

Cited by 70 publications

(55 citation statements)

References 22 publications

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“…While the molecular mechanism of 9p21 is unknown, its site of action has been confirmed. All studies have consistently shown the 9p21 risk variant relates to coronary atherosclerosis and only secondarily to myocardial infarction (32), (33), (34), (35). Some studies have also suggested 9p21 to be associated with the rate of progression of coronary atherosclerosis(32), (35).…”

Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

“…All studies have consistently shown the 9p21 risk variant relates to coronary atherosclerosis and only secondarily to myocardial infarction (32), (33), (34), (35). Some studies have also suggested 9p21 to be associated with the rate of progression of coronary atherosclerosis(32), (35). However, there are other studies(33), (36), which have not confirmed this correlation.…”

Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

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A genetic basis for coronary artery disease

Roberts¹

2015

Trends in Cardiovascular Medicine

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Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

Section: Discovery Of 9p21 the First Genetic Risk Variant Associatedmentioning

confidence: 99%

A genetic basis for coronary artery disease

Roberts¹

2015

Trends in Cardiovascular Medicine

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“…2 However, advances in genomics and proteomics, especially gene-expression profiling using microarray and quantitative real-time polymerase chain reaction (qPCR), have promoted the generation of many novel molecular biomarkers for AMI with potential clinical values. 3,4 Recently, microRNAs (miRNAs) have attracted extensive interest in the field of cardiovascular diseases. 5…”

mentioning

confidence: 99%

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Huang

Lü

et al. 2014

Circ Cardiovasc Genet

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A cute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. 1 Multiple conventional risk factors and serum atherosclerotic biomarkers have been established for coronary heart disease (CHD). 2 However, advances in genomics and proteomics, especially gene-expression profiling using microarray and quantitative real-time polymerase chain reaction (qPCR), have promoted the generation of many novel molecular biomarkers for AMI with potential clinical values. 3,4 Recently, microRNAs (miRNAs) have attracted extensive interest in the field of cardiovascular diseases. 5 Clinical Perspective on p 198MiRNAs are short, endogenous, noncoding RNAs that regulate gene expressions at the posttranscriptional level by binding to the 3′-untranslated regions of their target mRNAs. 6,7 MiRNAs have now emerged as key regulators of cardiac growth, vascular development, and angiogenesis. 8,9 Recent studies demonstrated that miRNAs can be detected in circulating blood and may be useful as disease biomarkers. 10,11 The levels and identities of circulating miRNAs in cardiovascular diseases have been evaluated in a series of studies. For instance, levels of some vascular and inflammation-associated miRNAs were found to be significantly lower in the plasma of 67 patients with CHD when compared with controls, 12 and the cardiac-specific miRNA, miR-208a, was only detectable in 33 patients with AMI and not Background-Circulating microRNAs ( miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations. Methods and Results-In the discovery stage, the plasma of 20 patients with AMI and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 patients with AMI and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays and further replicated in 150 patients with AMI and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in patients with AMI than in controls in both validation populations (P<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio, 4.71; 95% confidence interval, 2.96-7.48 and odds ratio, 4.27; 95% confidence interval, 2.84-6.41, respectively). Addition of the 2 miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% confidence interval, 0.787-0.856) to 0.871 (95% confidence interval, 0.842-0.900), with a net reclassification improvement of 20.45% (P<0.0001) and an integrated discrimination improvement of 0.16 (P<0.0001) for patients with AMI. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for coronary heart disease in human vascular endothelial cells. Conclusions-The...

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“…Более обнадеживающим выглядит предложение клинического использования генотипов локуса 9р21.3 для прогнозирования исходов у больных, пере-несших ИМ [13,14]. Однако этот вопрос также тре-бует дальнейшего изучения, что и предопределило цель нашего исследования -оценить возможность клинического применения данных генотипирования локуса 9р21.3 у больных ИМ.…”

Section: российский кардиологический журнал № 10 (114) | 2014unclassified

“…Более обоснованной в этой связи является использование генетических предик-торов в прогнозировании течения и исходов заболе-вания у больных, уже перенесших ИМ. Полученные нами данные согласуются с результатами других работ [13,14]. В частности, интеграция носительства аллеля риска С rs1333049 в шкалу риска GRACE улучшала прогнозирование сердечной смерти и повторного ИМ в течение полугода после перенесенного ОКС.…”

Section: рисunclassified

Clinical Significance of Coronary Artery Disease Genetic Markers: Reality or Far Future?

Шестерня¹,

Шульман²,

Никулина³

et al. 2015

Ross. kardiol. ž.

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Цель. Оценить возможность клинического применения данных генотипирова-ния локуса 9р21.3 у больных ИМ. Материал и методы. В исследование включено 500 больных ИМ в возра-сте ≤65 лет [Ме 54,0; Q 25 48,0; Q 75 59,0], в т. ч. 411 (82,2%) мужчин и 89 (17,8%) женщин, и данные 31 аутопсии -24 мужчин и 7 женщин в возра-сте ≤65 лет (57,87±5,92 лет) с верифицированным ИМ, как причиной смерти. Группа контроля состояла из 423 (79,1%) CLINICAL SIGNIFICANCE OF CORONARY ARTERY DISEASE GENETIC MARKERS: REALITY OR FAR FUTURE?Shesternya P. A.

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Influence of 9p21.3 Genetic Variants on Clinical and Angiographic Outcomes in Early-Onset Myocardial Infarction

Abstract: In early-onset myocardial infarction, the 9p21.3 variant rs1333040 affects the progression of coronary atherosclerosis and the probability of coronary artery revascularization during long-term follow-up.

Cited by 70 publications

References 22 publications

A genetic basis for coronary artery disease

A genetic basis for coronary artery disease

Circulating MicroRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations

Clinical Significance of Coronary Artery Disease Genetic Markers: Reality or Far Future?

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