AI Article Synopsis
- The study investigates the genetic factors associated with the susceptibility to atherosclerotic abdominal aortic aneurysms (AAAs) in Mexican patients, focusing on the HLA-DRB1 genes and MCP-1 gene.
- The research compares genotypes between 39 patients with AAAs and 99 controls, finding a significant association between certain HLA-DRB1 alleles and increased AAA risk.
- Results showed that specific alleles (HLA-DRB1*01 and HLA-DRB1*16) were more common in AAA patients, suggesting that genetic polymorphisms may play a role in the development of AAAs.
Article Abstract
Background: The pathogenesis of atherosclerotic abdominal aortic aneurysms (AAAs) 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 (HLAs, HLA-DRB1) with the susceptibility to develop AAA in Mexican patients and to initiate a pilot study of single-nucleotide polymorphisms (SNPs) rs1024611 in the monocyte chemoattractant protein-1 (MCP-1/CCL2) gene 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-One Lambda kit in 39 patients (69% men with a mean age of 72 years) and compared with 99 without the disease (60% men, mean age 65 years) (control group). Genotyping of rs1024611 in the MCP-1 gene was performed using TaqMan predesigned SNP genotyping assays in 27 patients with AAA (63% men, mean age of 71). Gene frequencies (gfs) and genotype frequencies (Gfs) were determined; categorical data were analyzed by nonparametric statistic test at significance level (P < 0.05), and odds ratios (ORs) were calculated using the STATA v14 software and StatCalc software Epi Info™ 7.2.2.2.
Results: Seventy-eight HLA-DRB1 alleles of patients with AAA 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 with 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 was 0.115 in the AAA and 0.025 in control group (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 women and younger than patients with other genotypes, and only one had a history of dyslipidemia.
Conclusions: The dissection and interpretation of an immunogenetic profile in patients with AAA 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 with an ethnically matched control group.
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| http://dx.doi.org/10.1016/j.avsg.2019.05.004 | DOI Listing |
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