Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis

Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of fiv...

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Main Authors: Yiming Shao, Junbing He, Feng Chen, Yujie Cai, Jianghao Zhao, Yao Lin, Zihan Yin, Hua Tao, Xin Shao, Pengru Huang, Mingkang Yin, Wenying Zhang, Zhou Liu, Lili Cui
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2016-09-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/447830
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author Yiming Shao
Junbing He
Feng Chen
Yujie Cai
Jianghao Zhao
Yao Lin
Zihan Yin
Hua Tao
Xin Shao
Pengru Huang
Mingkang Yin
Wenying Zhang
Zhou Liu
Lili Cui
author_facet Yiming Shao
Junbing He
Feng Chen
Yujie Cai
Jianghao Zhao
Yao Lin
Zihan Yin
Hua Tao
Xin Shao
Pengru Huang
Mingkang Yin
Wenying Zhang
Zhou Liu
Lili Cui
author_sort Yiming Shao
collection DOAJ
description Background: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.
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spelling doaj.art-255c58704bb14c31add555e40d2e56032022-12-22T03:16:58ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782016-09-013941247126110.1159/000447830447830Association Study Between Promoter Polymorphisms of ADAM17 and Progression of SepsisYiming ShaoJunbing HeFeng ChenYujie CaiJianghao ZhaoYao LinZihan YinHua TaoXin ShaoPengru HuangMingkang YinWenying ZhangZhou LiuLili CuiBackground: A disintegrin and metalloproteinase 17 (ADAM17) has been confirmed to play a significant role in the pathogenesis of sepsis. However, little is known about the clinical relevance of ADAM17 polymorphisms to sepsis onset and development. Methods: This study analyzed the associations of five ADAM17 promoter polymorphisms (rs55790676, rs12692386, rs11684747, rs1524668 and rs11689958) with sepsis (370 sepsis cases and 400 controls). Genotyping was performed using pyrosequencing and polymerase chain reaction-length polymorphism method. The ADAM17 expression was measured using the real-time PCR method and the concentrations of related cytokines were detected using enzyme-linked immunosorbent assay. Results: No associations were observed between these polymorphisms and sepsis susceptibility, while the rs12692386GA/GG genotypes were overrepresented among the patients with severe sepsis (P=0.002) or septic shock (P=0.0147) compared to those with sepsis subtype, suggesting a susceptible role of rs12692386A>G in the progression of sepsis. Moreover, ADAM17 expression was increased in the sepsis patients with the rs12692386GA/GG genotypes, accompanied by up-regulation of expression of the ADAM17 substrates (TNF-α, IL-6R and CX3CL1) and pro-inflammatory cytokines (IL-1β and IL-6). Conclusion: The present study has provided potentially valuable clinical evidence that the ADAM17 rs12692386 polymorphism is a functional variant that might be used as a relevant risk estimate for the progression of sepsis.http://www.karger.com/Article/FullText/447830ADAM17PolymorphismPro-inflammation cytokinesSepsisTNF-αIL-6RCX3CL1
spellingShingle Yiming Shao
Junbing He
Feng Chen
Yujie Cai
Jianghao Zhao
Yao Lin
Zihan Yin
Hua Tao
Xin Shao
Pengru Huang
Mingkang Yin
Wenying Zhang
Zhou Liu
Lili Cui
Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
Cellular Physiology and Biochemistry
ADAM17
Polymorphism
Pro-inflammation cytokines
Sepsis
TNF-α
IL-6R
CX3CL1
title Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
title_full Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
title_fullStr Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
title_full_unstemmed Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
title_short Association Study Between Promoter Polymorphisms of ADAM17 and Progression of Sepsis
title_sort association study between promoter polymorphisms of adam17 and progression of sepsis
topic ADAM17
Polymorphism
Pro-inflammation cytokines
Sepsis
TNF-α
IL-6R
CX3CL1
url http://www.karger.com/Article/FullText/447830
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