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.
BACKGROUND: Accumulating evidence suggests that the principal TNF-α converting enzyme, a disintegrin and metalloproteinase 17 (ADAM17), is involved in the development of humanabdominal 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 AAApatients. 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.
Authors: Thomas Schmitz-Rixen; M Keese; M Hakimi; A Peters; D Böckler; K Nelson; R T Grundmann Journal: Langenbecks Arch Surg Date: 2016-03-21 Impact factor: 3.445
Authors: Tong Jiao; Ye Yao; Bo Zhang; Da-Cheng Hao; Qing-Feng Sun; Jing-Bo Li; Chao Yuan; Bao Jing; Yun-Peng Wang; Hai-Yang Wang Journal: Biomed Res Int Date: 2017-03-05 Impact factor: 3.411
Authors: Silke Griepke; Emilie Grupe; Jes Sanddal Lindholt; Elizabeth Hvitfeldt Fuglsang; Lasse Bach Steffensen; Hans Christian Beck; Mia Dupont Larsen; Sissel Karoline Bang-Møller; Martin Overgaard; Lars Melholt Rasmussen; Kate Lykke Lambertsen; Jane Stubbe Journal: Front Cardiovasc Med Date: 2022-09-16