ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.
BACKGROUND
Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore, we evaluated atherosclerosis candidate genes for association with in-stent restenosis.


METHODS
We identified 46 consecutive cases that had undergone PCI with bare-metal stents who subsequently developed symptomatic in-stent restenosis of the target lesion (>/=75% luminal narrowing) within 6 months. Forty-six age-, race-, vessel-diameter- and sex-matched controls without in-stent restenosis after PCI with bare-metal stent were also identified. Single-nucleotide polymorphisms (SNPs, N=82) from 39 candidate atherosclerosis genes were genotyped. Multivariable logistic regression models were used to test for association.


RESULTS
Five SNPs were associated with in-stent restenosis. Three ALOX5AP SNPs were most strongly associated, two with increased risk (OR 3.74, p=0.01; OR 3.46, p=0.02), and the third with decreased risk of in-stent restenosis (OR 0.09, p=0.004). Two ALOX5AP haplotypes were associated with in-stent restenosis (HapB: OR 3.13, p=0.03); and a haplotype similar to HapA: OR 0.14, p=0.0009).


CONCLUSIONS
ALOX5AP, a gene within the inflammatory leukotriene pathway linked to and associated with coronary atherosclerosis, is also associated with in-stent restenosis. Genotyping these variants may help identify those at risk for in-stent restenosis who would benefit most from use of DES.
Shah
Svati H
SH
Department of Medicine, Duke University Medical Center, Durham, NC 27710, United States. svati.shah@duke.edu
Hauser
Elizabeth R
ER
Crosslin
David
D
Wang
Liyong
L
Haynes
Carol
C
Connelly
Jessica
J
Nelson
Sarah
S
Johnson
Jessica
J
Gadson
Shera
S
Nelson
Charlotte L
CL
Seo
David
D
Gregory
Simon
S
Kraus
William E
WE
Granger
Christopher B
CB
Goldschmidt-Clermont
Pascal
P
Newby
L Kristin
LK
D058927:5-Lipoxygenase-Activating Proteins; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000235:genetics* / Q000628:therapy; D023903:Coronary Restenosis / Q000235:genetics*; D054855:Drug-Eluting Stents / Q000009:adverse effects*; D005260:Female; D056726:Genetic Association Studies; D006083:Graft Occlusion, Vascular / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins