Investigation of an Immunogenetic profile in patients with Abdominal Aortic Aneurysms and possible applications in screening and surveillance

Abstract Introduction and objectives: The pathogenesis of atherosclerotic Abdominal Aortic Aneurysms (AAA) remains not fully understood. Histological analyses confirm chronic adventitial and medial inflammatory cell infiltration and its pathophysiology involves the upregulation of proteolytic pathways; added to this, genetic factors have been suggested to favor the susceptibility for AAA. The aim of the present study was to analyze the association between genetic polymorphism of the Class II Human Leukocyte Antigens (HLA-DRB1) with the susceptibility to develop AAA in Mexican patients and to initiate a pilot study of single-nucleotide polymorphisms (SNP) rs1024611 in the Monocyte chemoattractant protein-1 gene (MCP-1/CCL2) to investigate a possible role in the AAA pathogenesis. Methods In a cohort of patients with AAA, HLA molecular typing was completed for DRB1 loci with LABType SSO-OneLambda kit in 39 patients (69% males with a mean age of 72 years) and compared with 99 without the disease (60% males, mean age 65 years) (Control group). Genotyping of rs1024611 in the MCP-1 gene was performed using TaqMan Pre‐Designed single nucleotide polymorphism (SNP) genotyping assays in 27 AAA patients (63% males, mean age of 71). Gene (gf) and Genotype frequencies (Gf) were determined, categorical data were analyzed by nonparametric statistic test at significance level (p Results Seventy-eight HLA-DRB1 alleles of AAA patients and 198 from the control group were studied. We observed that the gf of HLA-DRB1*01 was 0.128 in the AAA group compared to 0.05 in the Control group [p=0.03, OR 2.6, 95% confidence interval (CI) 1.04-6.5], the gf of HLA-DRB1*16 were 0.115 in the AAA and 0.025 in CG (p=0.002, OR 5, 95% CI 1.6-16.9). The Gf for SNP rs1024611 were 0.51 in the GA genotype, 0.30 in AA, and 0.19 of GG. Four patients with the proinflammatory homozygous genotype GG (80%) were females and younger than patients with other genotypes, and only one had history of dyslipidemia. Conclusions The dissection and interpretation of an immunogenetic profile in AAA patients is an active and complex field of research that might assist in a more precise identification of those patients at genetic risk. Our study demonstrated increased frequencies of HLA-DRB1*01 and HLA-DRB1*16 alleles in Mexican patients with AAA compared to an ethnically matched control group.