Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm
Polymorphisms in the IL-6 and TNF-α gene are associated with an increased risk of abdominal aortic aneurysm
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DOI：
10.1016/j.ijcard.2020.12.051
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发表时间：
2021-03-04
影响因子：
3.5
通讯作者：
Huk, Ihor
中科院分区：
文献类型：
--
作者：
Jablonska, Agnieszka;Zagrapan, Branislav;Huk, Ihor
背景资料：腹主动脉瘤（AAA）是一种与炎症和细胞免疫反应相关的老年人群的复杂疾病。为探讨白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α单核苷酸多态性（SNPs）对AAA形成和进展风险的影响，测定AAA及其相关危险因素的频率。应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术对AAA患者和健康志愿者的TNF-α（-238G/A，rs361525; -572G/C，rs 1800796）和TNF-α（-308G/A，rs 1800629）基因进行了研究。结果：在IL-6 - 174 G/C单核苷酸多态性的至少一个等位基因中检测到突变与AAA发生的风险增加2倍相关（OR：2.08; 95%CI：1.15-3.76; p 0.014，在显性模型中）。观察到TNF-α-308 G/A基因型杂合子携带者中AAA发生率的风险增加（OR：2.06; 95% CI：1.17-3.62; p = 0.011，在超显性模型中）。IL-6 - 174 G/C和TNF-α-308 G/A SNP的野生型基因型在健康受试者中比AAA患者中更频繁地共存，并且与AAA风险降低相关（p < 0.001）。结论：IL-6 - 174 G/C和TNF-α-238 G/A基因多态性与腹主动脉瘤发病风险增加相关。(C)2020爱思唯尔B. V.保留所有权利。
Background: An abdominal aortic aneurysm (AAA) is a complex disease of the aging population that is associated with inflammation and the cellular immune response. To investigate the influence of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha single nucleotide polymorphisms (SNPs) on the risk of AAA formation and progression, the frequency of AAA and its associated risk factors were determined.Method: Four SNPs in the IL-6 (-174G/C, rs1800795; -572G/C, rs1800796) and TNF-alpha (-238G/A, rs361525; -308G/A, rs1800629) genes were studied by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in patients with AAA and healthy volunteers. The mRNA expression and plasma IL-6 and TNF-alpha levels were also determined.Results: A mutation detected in at least one allele of the IL-6 -174G/C SNP was associated with a 2-fold increased risk of AAA occurrence (OR: 2.08; 95% CI: 1.15-3.76; p 0.014, in the dominant model). An increased risk of AAA incidence among heterozygous carriers of the TNF-alpha - 308G/A genotype was observed (OR: 2.06; 95% CI: 1.17-3.62; p = 0.011, in the overdominant model). The wild-type genotypes of the IL-6 -174G/C and the TNF-alpha -308G/A SNPs coexisted more frequently in healthy subjects than in AAA patients and was associated with decreased risk of AAA (p < 0.001). Moreover, elevated levels of IL-6 and TNF-alpha were associated with an increased risk of hypertension (p < 0.001 and p = 0.022, respectively).Conclusions: The IL-6 -174G/C and the TNF-alpha-238G/A gene polymorphisms are associated with an increased risk of abdominal aortic aneurysm development. (C) 2020 Elsevier B.V. All rights reserved.