Reduced risk of recurrent myocardial infarction in homozygous carriers of the chromosome 9p21 rs1333049 C risk allele in the contemporary percutaneous coronary intervention era: a prospective observational study

Objectives Chromosome 9p21 single nucleotide polymorphism (SNP) is a susceptibility variant for acute myocardial infarction (AMI) in the primary prevention setting. However, it is controversial whether this SNP is also associated with recurrent myocardial infarction (ReMI) in the secondary prevention setting. The purpose of this study is to evaluate the impact of chromosome 9p21 SNP on ReMI in patients receiving secondary prevention programmes after AMI. Design A prospective observational study. Setting Osaka Acute Coronary Insufficiency Study (OACIS) in Japan. Participants 2022 patients from the OACIS database. Interventions Genotyping of the 9p21 rs1333049 variant. Primary outcome measures ReMI event after survival discharge for 1 year. Results A total of 43 ReMI occurred during the 1 year follow-up period. Although the rs1333049 C allele had an increased susceptibility to their first AMI in an additive model when compared with 1373 healthy controls (OR 1.20, 95% CI 1.09 to 1.33, p=2.3*10−4), patients with the CC genotype had a lower incidence of ReMI at 1 year after discharge of AMI (log-rank p=0.005). The adjusted HR of the CC genotype as compared with the CG/GG genotypes was 0.20 (0.06 to 0.65, p=0.007). Subgroup analysis demonstrated that the association between the rs1333049 CC genotype and a lower incidence of 1 year ReMI was common to all subgroups. Conclusions Homozygous carriers of the rs1333049 C allele on chromosome 9p21 showed a reduced risk of 1 year ReMI in the contemporary percutaneous coronary intervention era, although the C allele had conferred susceptibility to their first AMI.

[1]  C McRae,et al.  Myocardial infarction. , 2019, Australian family physician.

[2]  I. Komuro,et al.  Clinical impact of acute hyperglycemia on development of diabetes mellitus in non-diabetic patients with acute myocardial infarction. , 2014, Journal of cardiology.

[3]  I. Komuro,et al.  Living alone and risk of cardiovascular events following discharge after acute myocardial infarction in Japan. , 2013, Journal of cardiology.

[4]  I. Komuro,et al.  Elevated serum heart-type fatty acid-binding protein in the convalescent stage predicts long-term outcome in patients surviving acute myocardial infarction. , 2013, Circulation Journal.

[5]  T. Assimes,et al.  Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis. , 2013, Journal of the American College of Cardiology.

[6]  I. Komuro,et al.  Impact of beta blockade therapy on long-term mortality after ST-segment elevation acute myocardial infarction in the percutaneous coronary intervention era. , 2013, The American journal of cardiology.

[7]  E. Boerwinkle,et al.  Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. , 2012, Circulation journal : official journal of the Japanese Circulation Society.

[8]  R. Tsunoda,et al.  Recurrence of angina pectoris after percutaneous coronary intervention is reduced by statins in Japanese patients. , 2011, Journal of cardiology.

[9]  Swneke D. Bailey,et al.  The Effect of Chromosome 9p21 Variants on Cardiovascular Disease May Be Modified by Dietary Intake: Evidence from a Case/Control and a Prospective Study , 2011, PLoS medicine.

[10]  D. Altshuler,et al.  Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in early-onset myocardial infarction. , 2011, Journal of the American College of Cardiology.

[11]  Thomas W. Mühleisen,et al.  Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease , 2011, Nature Genetics.

[12]  R. McPherson,et al.  Gene dosage of the common variant 9p21 predicts severity of coronary artery disease. , 2010, Journal of the American College of Cardiology.

[13]  F. Van de Werf,et al.  A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study. , 2010, European heart journal.

[14]  J. Ferrières,et al.  Genetic determinants of response to clopidogrel and cardiovascular events. , 2009, The New England journal of medicine.

[15]  Janice D Nunnelee,et al.  Review of an Article: The international Warfarin Pharmacogenetics Consortium (2009). Estimation of the warfarin dose with clinical and pharmacogenetic data. NEJM 360 (8): 753-64. , 2009, Journal of vascular nursing : official publication of the Society for Peripheral Vascular Nursing.

[16]  J. Ornato,et al.  2009 Focused Updates: ACC/AHA Guidelines for the Management of Patients With ST‐Elevation Myocardial Infarction (Updating the 2004 Guideline and 2007 Focused Update) and ACC/AHA/SCAI Guidelines on Percutaneous Coronary Intervention (Updating the 2005 Guideline and 2007 Focused Update) , 2009, Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions.

[17]  R. Altman,et al.  Estimation of the warfarin dose with clinical and pharmacogenetic data. , 2009, The New England journal of medicine.

[18]  Alberto Piazza,et al.  Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants , 2009, Nature Genetics.

[19]  B. Horne,et al.  Association of Variation in the Chromosome 9p21 Locus With Myocardial Infarction Versus Chronic Coronary Artery Disease , 2008, Circulation. Cardiovascular genetics.

[20]  R. Collins,et al.  SLCO1B1 variants and statin-induced myopathy--a genomewide study. , 2008, The New England journal of medicine.

[21]  Ludwig A Hothorn,et al.  Repeated Replication and a Prospective Meta-Analysis of the Association Between Chromosome 9 p 21 . 3 and Coronary Artery Disease , 2008 .

[22]  G. Ginsburg,et al.  Taking cardiovascular genetic association studies to the next level. , 2007, Journal of the American College of Cardiology.

[23]  Kari Stefansson,et al.  A common variant on chromosome 9p21 affects the risk of myocardial infarction. , 2007, Science.

[24]  C. Gieger,et al.  Genomewide association analysis of coronary artery disease. , 2007, The New England journal of medicine.

[25]  Jonathan C. Cohen,et al.  A Common Allele on Chromosome 9 Associated with Coronary Heart Disease , 2007, Science.

[26]  Yusuke Nakamura,et al.  A high-throughput SNP typing system for genome-wide association studies , 2001, Journal of Human Genetics.

[27]  L. Berkman,et al.  Genetic susceptibility to death from coronary heart disease in a study of twins. , 1994, The New England journal of medicine.

[28]  A. Ibrahim,et al.  Acute myocardial infarction. , 2014, Critical care clinics.

[29]  I. Komuro,et al.  Low levels of serum n-3 polyunsaturated fatty acids are associated with worse heart failure-free survival in patients after acute myocardial infarction. , 2013, Circulation journal : official journal of the Japanese Circulation Society.

[30]  Kenneth A Ellenbogen,et al.  2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (Updating the 2006 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. , 2011, Journal of the American College of Cardiology.

[31]  Xingyu,et al.  The Effect of Chromosome 9 p 21 Variants on Cardiovascular Disease May Be Modified by Dietary Intake : Evidence from a Case / Control and a Prospective Study , 2011 .

[32]  Nomenclature and criteria for diagnosis of ischemic heart disease. Report of the Joint International Society and Federation of Cardiology/World Health Organization task force on standardization of clinical nomenclature. , 1979, Circulation.