Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease: Associação independente da variante rs1333049, no locus 9p21, com a doença coronária, numa população portuguesa

M.I. Mendonça, R.P. Dos Reis, A. Pereira, H. Café, M. Serráo, A.C. Sousa, A.I. Freitas, G. Guerra, S. Freitas, C. Freitas, I. Ornelas, A. Brehm, J.J. Araújo

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Introduction: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. Aim: To investigate whether the SNP rsl333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. Methods: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.7±8.9 years, 79.9% male) and 683 controls without coronary disease (mean age 53.3±10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. Results: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR=1.33; p=0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR=1.34, p=0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR=1.05, p=0.670). After logistic regression analysis, the CC genotype remained in the equation with 0R=1.7; p=0.018 and CG with OR=I.5, p=0.048. Conclusion: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.
Original languageEnglish
Pages (from-to)575-591
Number of pages17
JournalRevista Portuguesa de Cardiologia
Issue number6
Publication statusPublished - 2011


  • Coronary artery disease
  • Genetic polymorphisms
  • Locus 9p21
  • Risk factors
  • biological marker
  • adult
  • aged
  • allele
  • article
  • chromosome 9p
  • confidence interval
  • controlled study
  • coronary artery disease
  • coronary risk
  • female
  • gene locus
  • genetic analysis
  • genetic association
  • genetic variability
  • genotype
  • human
  • logistic regression analysis
  • major clinical study
  • male
  • nucleotide sequence
  • polymerase chain reaction
  • Portugal
  • risk factor
  • single nucleotide polymorphism
  • Case-Control Studies
  • Chromosomes, Human, Pair 9
  • Coronary Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide


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