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. 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.
Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
You
Y
Li
Cheng
C
Yang
Guoda
G
Ma
Lili
L
Cui
Xuefeng
X
Gu
Yanyan
Y
Chen
Bin
B
Zhao
Haiyang
H
Wang
Keshen
K
Li
D051722:ADAM Proteins / Q000235:genetics*; D000072198:ADAM17 Protein; D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics
D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human