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纤维连接蛋白 1 基因多态性(rs145233125、rs11070646、rs201170905)与中国汉族人群 Debakey Ⅲ型主动脉夹层的易感性和临床预后相关。

Fibrillin-1 Gene Polymorphisms (rs145233125, rs11070646, rs201170905) Are Associated With the Susceptibility and Clinical Prognosis of DeBakey Type III Aortic Dissection in Chinese Han Population.

机构信息

Department of Cardiology, Fuyang Tumor Hospital, Fuyang, China.

Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

出版信息

J Cardiovasc Pharmacol. 2022 Jul 1;80(1):118-124. doi: 10.1097/FJC.0000000000001282.

Abstract

We aim to investigate whether genetic variants of the Fibrillin-1 (FBN1) gene were associated with DeBakey type III aortic dissection (AD) and its clinical prognosis in Chinese Han population. Three single-nucleotide polymorphisms (SNPs) (rs145233125, rs11070646, rs201170905) in FBN1 were analyzed in patients with DeBakey type III AD (159) and healthy subjects (216). Gene-environment interactions were evaluated to use generalized multifactor dimensionality reduction. Haplotype analysis of the 3 SNPs in the FBN1 gene was performed by Haploview software. Patients were followed up for average 4 years. G carriers of rs11070646 and rs201170905 in FBN1 have an increased risk of DeBakey type III AD. The interaction of FBN1 and environmental factors facilitated to the increased risk of DeBakey type III AD (cross-validation consistency = 10/10, P = 0.001). One of the most common haplotypes revealed an increased risk of DeBakey type III AD (CGG, P = 0.009). Recessive models of rs145233125 CC genotype ( P < 0.05) and rs201170905 GG genotype ( P < 0.001) were associated with an increased risk of death and recurrent chest pain of DeBakey type III AD. In conclusions, FBN1 gene polymorphisms contribute to DeBakey type III AD susceptibility. The interactions of gene and environment are related with the risk of DeBakey type III AD. C carriers of rs145233125 and G carriers of rs201170905 may be the adverse prognostic indicators of death and recurrent chest pain in DeBakey type III AD.

摘要

我们旨在研究纤维连接蛋白 1(FBN1)基因的遗传变异是否与中国汉族人群的 DeBakey Ⅲ型主动脉夹层(AD)及其临床预后相关。在 DeBakey Ⅲ型 AD 患者(159 例)和健康对照者(216 例)中分析了 FBN1 中的三个单核苷酸多态性(SNP)(rs145233125、rs11070646、rs201170905)。采用广义多因子降维法评估基因-环境相互作用。使用 Haploview 软件对 FBN1 基因中这 3 个 SNP 的单倍型进行分析。对患者进行了平均 4 年的随访。FBN1 中 rs11070646 和 rs201170905 的 G 携带者患 DeBakey Ⅲ型 AD 的风险增加。FBN1 与环境因素的相互作用促进了 DeBakey Ⅲ型 AD 的发病风险(交叉验证一致性=10/10,P=0.001)。最常见的单倍型之一显示出患 DeBakey Ⅲ型 AD 的风险增加(CGG,P=0.009)。rs145233125 CC 基因型(P<0.05)和 rs201170905 GG 基因型(P<0.001)的隐性模型与 DeBakey Ⅲ型 AD 死亡和复发性胸痛的风险增加相关。总之,FBN1 基因多态性与 DeBakey Ⅲ型 AD 易感性有关。基因与环境的相互作用与 DeBakey Ⅲ型 AD 的发病风险有关。rs145233125 的 C 携带者和 rs201170905 的 G 携带者可能是 DeBakey Ⅲ型 AD 死亡和复发性胸痛的不良预后指标。

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