FBN1 polymorphisms in patients with the dilatative pathology of the ascending thoracic aorta

Abstract

Objectives: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely, rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study for dilatative pathology of the ascending thoracic aorta (DPATA) from Lithuanians.

Methods: We studied 312 patients who had undergone aortic reconstructive surgery for DPATA. These patients were sub-divided according to the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii) post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n = 79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was recruited from a random sample screened within epidemiological studies of the Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase-chain-reaction amplification.

Results: Patients within the aortic dissection sub-group had significantly higher minor allele frequencies in all five FBN1 single nucleotide polymorphism (SNPs) studied versus reference group subjects (P < 0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly higher in those with aortic aneurysm when compared with the reference group (P = 0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR 1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes with each phenotype of DPATA was assessed using logistic regression models adjusted for gender, age and hypertension. The additive model best fitted SNPs rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub-group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR 2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95% 2.06-9.01). There were no significant associations between all studied FBN1 SNPs and post-stenotic or bicuspid aortic dilatation.

Conclusions: Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection.

Keywords: Aneurysm; Dissection; Fibrillin-1; Polymorphisms; Thoracic aorta.