C-reactive protein polymorphism rs3091244 is associated with abdominal aortic aneurysm

• Published in: Journal of vascular surgery 2014-11, Vol.60 (5), p.1332-1339
• Main Authors: Saratzis, Athanasios, MBBS, MRCS, Bown, Matthew, MD, FRCS, Wild, Ben, MD, MRCS, Sayers, Robert D., MD, FRCS, Nightingale, Peter, PhD, Smith, Jacqueline, BSc, MSc, Johnson, Christopher, BSc, Kitas, George, MD, PhD, FRCP
• Format: Article
• Language: English
• Subjects: Aged; Aortic Aneurysm, Abdominal - blood; Aortic Aneurysm, Abdominal - diagnosis; Aortic Aneurysm, Abdominal - epidemiology; Aortic Aneurysm, Abdominal - genetics; C-Reactive Protein - analysis; C-Reactive Protein - genetics; Case-Control Studies; Chi-Square Distribution; Comorbidity; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Greece - epidemiology; Heterozygote; Homozygote; Humans; Inflammation Mediators - blood; Male; Middle Aged; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Surgery; United Kingdom - epidemiology
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1016/j.jvs.2013.07.105

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; I2  = 83.1%; P  = .04). Conclusions The rare