Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm

Background: Accumulating evidence suggests that the principal TNF-α converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved in the development of human abdominal aortic aneurysm (AAA). However, the association between ADAM17 gene polymorphisms and AAA has not been explored. T...

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Main Authors: You Li, Cheng Yang, Guoda Ma, Lili Cui, Xuefeng Gu, Yanyan Chen, Bin Zhao, Haiyang Wang, Keshen Li
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2014-05-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/358708
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author You Li
Cheng Yang
Guoda Ma
Lili Cui
Xuefeng Gu
Yanyan Chen
Bin Zhao
Haiyang Wang
Keshen Li
author_facet You Li
Cheng Yang
Guoda Ma
Lili Cui
Xuefeng Gu
Yanyan Chen
Bin Zhao
Haiyang Wang
Keshen Li
author_sort You Li
collection DOAJ
description Background: Accumulating evidence suggests that the principal TNF-α converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved in the development of human abdominal aortic aneurysm (AAA). However, the association between ADAM17 gene polymorphisms and AAA has not been explored. The present study was aimed to determine the association between ADAM17 promoter polymorphisms and AAA. Methods: A total of 316 patients with AAA and 306 age-matched healthy controls were enrolled in this study. Two ADAM17 promoter polymorphisms (rs12692386 and rs1524668) were determind. Real-time PCR was employed to detect the expression of ADAM17. Results: Overall, there was a significant difference in the frequency of the genotype rs12692386 between the AAA and control subjects (P=0.0096). Furthermore, men with the rs12692386 AG genotype conferred a higher risk of developing AAA (P=0.0058). Additionally, the rs12692386 mutated AG genotype of ADAM17 was significantly associated with increased ADAM17 expression (P=0.035) and TNF-α production (P=0.042) in AAA patients. In contrast, the allele frequency of rs1524668 was not statistically associated with AAA. Conclusions: Our findings indicate a positive association between the rs12692386 polymorphism of ADAM17 and AAA. This new knowledge about ADAM17 identifies a role for ADAM17 in the pathophysiology of AAA and has important clinical implications with regard to potential therapeutics.
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spelling doaj.art-bcec8c8661ba45e5be736f79eef4e7f22022-12-22T02:02:11ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-05-013351426143810.1159/000358708358708Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic AneurysmYou LiCheng YangGuoda MaLili CuiXuefeng GuYanyan ChenBin ZhaoHaiyang WangKeshen LiBackground: Accumulating evidence suggests that the principal TNF-α converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved in the development of human abdominal aortic aneurysm (AAA). However, the association between ADAM17 gene polymorphisms and AAA has not been explored. The present study was aimed to determine the association between ADAM17 promoter polymorphisms and AAA. Methods: A total of 316 patients with AAA and 306 age-matched healthy controls were enrolled in this study. Two ADAM17 promoter polymorphisms (rs12692386 and rs1524668) were determind. Real-time PCR was employed to detect the expression of ADAM17. Results: Overall, there was a significant difference in the frequency of the genotype rs12692386 between the AAA and control subjects (P=0.0096). Furthermore, men with the rs12692386 AG genotype conferred a higher risk of developing AAA (P=0.0058). Additionally, the rs12692386 mutated AG genotype of ADAM17 was significantly associated with increased ADAM17 expression (P=0.035) and TNF-α production (P=0.042) in AAA patients. In contrast, the allele frequency of rs1524668 was not statistically associated with AAA. Conclusions: Our findings indicate a positive association between the rs12692386 polymorphism of ADAM17 and AAA. This new knowledge about ADAM17 identifies a role for ADAM17 in the pathophysiology of AAA and has important clinical implications with regard to potential therapeutics.http://www.karger.com/Article/FullText/358708ADAM17Abdominal aortic aneurysmPolymorphism
spellingShingle You Li
Cheng Yang
Guoda Ma
Lili Cui
Xuefeng Gu
Yanyan Chen
Bin Zhao
Haiyang Wang
Keshen Li
Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
Cellular Physiology and Biochemistry
ADAM17
Abdominal aortic aneurysm
Polymorphism
title Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
title_full Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
title_fullStr Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
title_full_unstemmed Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
title_short Analysis of ADAM17 Polymorphisms and Susceptibility to Sporadic Abdominal Aortic Aneurysm
title_sort analysis of adam17 polymorphisms and susceptibility to sporadic abdominal aortic aneurysm
topic ADAM17
Abdominal aortic aneurysm
Polymorphism
url http://www.karger.com/Article/FullText/358708
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