title: C-reactive protein polymorphism rs3091244 is associated with abdominal aortic aneurysm.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) formation involves an inflammatory process with a strong genetic background. C-reactive protein (CRP) regulates inflammation and is elevated in patients with AAA. The aim of this study was to investigate the association of the triallelic (C, A, and T alleles) rs3091244 functional CRP single nucleotide polymorphism (SNP) with AAA.
  
  
  METHODS
  This was a case-control study involving two independent populations: 351 AAA patients (mean aortic diameter, 6.25 ± 1.47 cm) and 391 controls (mean diameter, 2.4 ± 0.2 cm) were recruited from Greece (the main cohort); and 371 patients (mean diameter, 5.4 ± 1.0 cm) and 362 controls (mean diameter, 2.4 ± 0.6 cm) were recruited from the United Kingdom (replication cohort). The frequency of the functional triallelic (C, T, and A alleles) rs3091244 polymorphism was analyzed in univariate and adjusted (for cardiovascular risk factors) analyses, assuming that the rare T and A alleles have similar functional properties (pooled analysis for T and A). Three groups were constructed: group A included those with the rare T and A alleles (genotypes TT, AA, and TA), group B included heterozygotes for the C allele (CT, CA), and group C included C allele homozygotes (CC, reference genotype). Finally, meta-analysis of the two populations was performed together with previously reported results.
  
  
  RESULTS
  Genotype distributions differed significantly between cases and controls in both cohorts (P < .001 and P = .001). Adjusted analysis (for all aneurysm-related risk-factors) showed an estimated odds ratio of 4.88 (95% confidence interval [CI], 2.96-8.04) for SNP group A and 2.38 (95% CI, 1.69-3.36) for SNP group B (P < .001 in both cases) in the initial cohort and 2.07 (95% CI, 1.33-3.21) for SNP group A and 1.70 (95% CI, 1.21-2.39) for SNP group B (P = .001 and .002) in the replication cohort. The SNP group A patients among the main cohort also had higher CRP levels (median, 26; interquartile range, 17-52 mg/L vs median, 4; interquartile range, 4-12 mg/L; P < .001). Aneurysms >5.5 cm were significantly more frequent among the SNP groups A and B compared with C allele homozygotes both in the main and the replication cohorts (P < .001 and P = .001, respectively). Meta-analysis of the two populations with previously reported results showed a positive association between minor-allele and aneurysm presence with an odds ratio of 1.47 (95% CI, 1.01-2.14; I(2) = 83.1%; P = .04).
  
  
  CONCLUSIONS
  The rare T and A alleles were significantly related with AAA presence in both populations and correlated with higher CRP levels and AAA diameter.
authors.affiliation: Department of Vascular Surgery, Aristotle University, Thessaloniki, Greece; Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom. Electronic address: a_saratzis@yahoo.gr.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Saratzis
authors.affiliation: Department of Cardiovascular Sciences and National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Bown
authors.affiliation: Department of Cardiovascular Sciences and National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Wild
authors.affiliation: Department of Cardiovascular Sciences and National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, University of Leicester, Leicester, United Kingdom.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Sayers
authors.affiliation: Wolfson Computer Laboratory, University Hospitals Birmingham, Birmingham, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.affiliation: Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Smith
authors.affiliation: Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Johnson
authors.affiliation: Department of Research and Development, Dudley Group of Hospitals, Dudley, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Kitas
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015897:Comorbidity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D018836:Inflammation Mediators; D002097:C-Reactive Protein