title: Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To investigate whether the SNP rs1333049 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 53.71 +/- 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 OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unidade de Investigação e Serviço de Cardiologia do Hospital Nélio de Mendonça (SESARAM), Funchal, Portugal. dep.card@srs.pt
authors.forename: Isabel
authors.initials: I
authors.lastname: Mendonça
authors.forename: Roberto Palma
authors.initials: RP
authors.lastname: dos Reis
authors.forename: Andreia
authors.initials: A
authors.lastname: Pereira
authors.forename: Hugo
authors.initials: H
authors.lastname: Café
authors.forename: Marco
authors.initials: M
authors.lastname: Serrão
authors.forename: Ana Célia
authors.initials: AC
authors.lastname: Sousa
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Freitas
authors.forename: Graça
authors.initials: G
authors.lastname: Guerra
authors.forename: Sónia
authors.initials: S
authors.lastname: Freitas
authors.forename: Carolina
authors.initials: C
authors.lastname: Freitas
authors.forename: Ilídio
authors.initials: I
authors.lastname: Ornelas
authors.forename: António
authors.initials: A
authors.lastname: Brehm
authors.forename: José Jorge
authors.initials: JJ
authors.lastname: Araújo
mesh_terms: D016022:Case-Control Studies; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide