Anaya-Ayala Javier E, Escamilla-Tilch Monica, Granados Julio, Hernandez-Dono Susana, Hernandez-Sotelo Kemberly, Lozano-Corona Rodrigo, Ruiz-Gomez Daniela, Garcia-Toca Manuel, Hinojosa Carlos A
Department of Surgery, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubirán, Section of Vascular Surgery and Endovascular Therapy, Mexico City, Mexico; Division for Postgraduate studies, Universidad Nacional Autonoma de Mexico, Faculty of Medicine, Master and Doctoral degree program, Mexico City, Mexico.
Centro Medico Nacional 20 de Noviembre, Biochemistry Unit, Mexico City, Mexico.
Ann Vasc Surg. 2020 Jan;62:57-62. doi: 10.1016/j.avsg.2019.05.004. Epub 2019 Jun 12.
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.
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.
Seventy-eight HLA-DRB1 alleles of patients with AAA and 198 from the control group were studied. We observed that the gf of HLA-DRB101 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-DRB116 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.
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-DRB101 and HLA-DRB116 alleles in Mexican patients with AAA compared with an ethnically matched control group.
动脉粥样硬化性腹主动脉瘤（AAA）的发病机制仍未完全明确。组织学分析证实存在慢性外膜和中膜炎性细胞浸润，其病理生理学涉及蛋白水解途径的上调；此外，有研究表明遗传因素会增加患AAA的易感性。本研究旨在分析Ⅱ类人类白细胞抗原（HLAs，HLA-DRB1）基因多态性与墨西哥患者患AAA易感性之间的关联，并启动一项关于单核细胞趋化蛋白-1（MCP-1/CCL2）基因单核苷酸多态性（SNP）rs1024611的初步研究，以探讨其在AAA发病机制中的可能作用。
在一组AAA患者队列中，使用LABType SSO-One Lambda试剂盒对39例患者（69%为男性，平均年龄72岁）的DRB1位点进行HLA分子分型，并与99例无该病患者（60%为男性，平均年龄65岁）（对照组）进行比较。使用TaqMan预设计SNP基因分型检测对27例AAA患者（63%为男性，平均年龄71岁）的MCP-1基因rs1024611进行基因分型。确定基因频率（gfs）和基因型频率（Gfs）；分类数据采用非参数统计检验，显著性水平为P < 0.05，并使用STATA v14软件和StatCalc软件Epi Info™ 7.2.2.2计算比值比（ORs）。
研究了AAA患者的78个HLA-DRB1等位基因和对照组的198个等位基因。我们观察到，AAA组中HLA-DRB101的基因频率为0.128，而对照组为0.05（P = 0.03，OR：2.6，95%置信区间[CI]：1.04 - 6.5）；AAA组中HLA-DRB116的基因频率为0.115，对照组为0.025（P = 0.002，OR：5，95% CI：1.6 - 16.9）。SNP rs1024611的基因型频率在GA基因型中为0.51，AA中为0.30，GG中为0.19。4例具有促炎纯合基因型GG的患者（80%）为女性，且比其他基因型患者年轻，只有1例有血脂异常病史。
剖析和解读AAA患者的免疫遗传特征是一个活跃且复杂的研究领域，可能有助于更精确地识别有遗传风险的患者。我们的研究表明，与种族匹配的对照组相比，墨西哥AAA患者中HLA-DRB101和HLA-DRB116等位基因的频率增加。
