Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

Peng, Wen; Lü, Lin; Zhang, Qi; Zhang, Rui Yan; Wang, Ling Jie; Yan, Xin; Chen, Qiujing; Shen, Wei Feng

doi:10.1515/cclm.2009.215

Cited by 20 publications

(20 citation statements)

References 24 publications

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“…The results from European registries may be not in concordance with studies performed in other populations [23], [24]. The effect sizes of specific genotypes may be strongly related to genetic background as well as to environmental factors.…”

Section: Discussioncontrasting

confidence: 57%

“…Therefore it is essential to validate the results of genetic studies in regional populations. In Han Chinese patients with STEMI, no differences were found between the 9p21 locus genotypes in 2-year event-free survival (cardiac death, non-fatal MI, recurrent angina, or heart failure requiring hospitalization), [24]. Similarly, patients from Post-Myocardial Infarction Study (New Zealand, 9-year follow-up) had genotype-dependent variation neither in total mortality nor in hospital admissions due to reinfarctions or heart failure [23].…”

Section: Discussionmentioning

confidence: 96%

“…In the GRACE registry that was performed in Europe (n = 3247, patients with all forms of an acute coronary syndrome, 6 months of follow-up), the C allele of the rs1333049 polymorphism was independently associated with recurrent myocardial infarction or cardiac death [22]. No association with outcome was found in the population of the Post-Myocardial Infarction study (New Zealand, n = 816, median follow-up 9 years) or in Han Chinese patients with first ST-segment elevation myocardial infarction (STEMI, n = 520, median follow-up 29 months) [23]–[24]. On the contrary, there is an increasing number of reports with surprisingly improved prognosis in patients with established CAD, or after an acute coronary syndrome, who carry alleles associated with a higher risk of atherosclerosis (25–27).…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

et al. 2014

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ObjectiveThe rs10757278, rs1333049 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus associated with a prevalence of acute coronary syndromes (ACS). Reports concerning their association with long-term outcome after an ACS are equivocal. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI).Materials and methodsWe performed a retrospective analysis of data collected prospectively in 2 independent registries of consecutive patients with STEMI (derivation and validation group). Genotyping was performed with the TaqMan method. The analyzed end-point was total mortality.ResultsThe derivation group comprised 589 patients: 25.3% female (n = 149), mean age 62.4±12.0 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (GRACE risk score ≥155 points, n = 238), homozygotes associated with higher risk for ACS had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with the high-risk genotype (a homozygote of high risk for ACS or a heterozygote) was: HR = 2.2 (1.15–4.2) for the rs10757278 polymorphism, HR = 2.7 (95% CI 1.3–5.4) for the rs4977574 one and HR = 2.3 (1.2–4.5) for the rs1333049 one (Cox proportional hazards model). Survival analysis in the validation group (n = 365) showed a clear trend towards better prognosis in GG homozygotes of the rs10757278 SNP, which confirms our initial results (p = 0.09, log-rank test).ConclusionsThe 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. The genotypes associated with higher risk for ACS show a protective effect in terms of further survival (instead of a deteriorating prognosis, as reported previously). This finding, due to the very high size of the effect, could potentially be applied to clinical practice, if appropriate methods are elaborated.

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Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

et al. 2014

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“…In the GRACE registry that was performed in Europe (n = 3247, patients with all forms of an acute coronary syndrome, 6 months of follow-up), C allele of the rs1333049 polymorphism was independently associated with recurrent myocardial infarction or cardiac death [21]. No association with outcome was found in the population of the Post-Myocardial Infarction study (New Zealand, n = 816, median follow-up 9 years) or in Han Chinese patients with first ST-segment elevation myocardial infarction (STEMI, n = 520, median follow-up 29 months) [22]–[23]. The discrepancies were not related to type of treatment.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

et al. 2013

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ObjectiveThe rs1333049, rs10757278 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus that are associated with prevalence of acute coronary syndromes (ACS). The rs1333049 SNP was also associated with cardiac outcome 6 months post ACS. No data concerning their association with long term prognosis after myocardial infarction is available. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively.Materials and MethodsWe performed a retrospective analysis of data collected prospectively in a registry of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with a TaqMan method. The analyzed end-point was total 5-year mortality.ResultsThe study group comprised 589 patients: 25.3% of females (n = 149), mean age 62.4±11.9 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (Grace risk score ≥155 points, n = 238), low-risk homozygotes had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with high-risk genotype (high-risk homozygote or heterozygote) was: HR = 2.9 (95%CI 1.4–6.1) for the rs4977574 polymorphism, HR = 2.6 (1.25–5.3) for the rs1333049 one and HR = 2.35 (1.2–4.6) for the rs10757278 one (Cox proportional hazards model).ConclusionsThe 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. This finding, due to very high effect size, could potentially be applied into clinical practice, if appropriate methods are elaborated.

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“…Genome-wide association studies (GWAS) have found that single nucleotide polymorphisms (SNPs) on chromosome 9p21 (Chr9p21) affect susceptibility to coronary artery disease (CAD) in Caucasian population [1], [2], [3], [4], and these associations have been reproduced in other populations [5], [6], [7], [8]. However, the mechanisms of Chr9p21 for CAD remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Methylation of p15INK4b and Expression of ANRIL on Chromosome 9p21 Are Associated with Coronary Artery Disease

Zhuang

Peng

et al. 2012

PLoS ONE

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BackgroundGenome-wide association studies have identified that multiple single nucleiotide polymorphisms on chromosome 9p21 are tightly associated with coronary artery disease (CAD). However, the mechanism linking this risk locus to CAD remains unclear.Methodology/Principal FindingsThe methylation status of six candidate genes (BAX, BCL-2, TIMP3, p14ARF, p15INK4b and p16INK4a) in 205 patients and controls who underwent coronary angiography were analyzed by quantitative MethyLight assay. Rs10757274 was genotyped and expression of INK4/ARF and antisense non-coding RNA in the INK4 locus (ANRIL) was determined by real-time RT-PCR. Compared with controls, DNA methylation levels at p15INK4b significantly increased in CAD patients (p = 0.006). To validate and dissect the methylation percentage of each target CpG site at p15INK4b, pyrosequencing was performed, finding CpG +314 and +332 remarkably hypermethylated in CAD patients. Further investigation determined that p15INK4b hypermethylation prevalently emerged in lymphocytes of CAD patients (p = 0.013). The rs10757274 genotype was significantly associated with CAD (p = 0.003) and GG genotype carriers had a higher level of ANRIL exon 1–5 expression compared among three genotypes (p = 0.009). There was a stepwise increase in p15INK4b and p16INK4a methylation as ANRIL exon 1–5 expression elevated (r = 0.23, p = 0.001 and r = 0.24, p = 0.001, respectively), although neither of two loci methylation was directly linked to rs10757274 genotype.Conclusions/Significance p15INK4b methylation is associated with CAD and ANRIL expression. The epigenetic changes in p15INK4b methylation and ANRIL expression may involve in the mechanisms of chromosome 9p21 on CAD development.

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Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

Cited by 20 publications

References 24 publications

Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

Polymorphism of 9p21.3 Locus Is Associated with 5-Year Survival in High-Risk Patients with Myocardial Infarction

Methylation of p15INK4b and Expression of ANRIL on Chromosome 9p21 Are Associated with Coronary Artery Disease

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