Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention.
Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The GENetic DEterminants of Restenosis (GENDER) study included 3104 patients treated with successful PCI. Target vessel revascularization (TVR) was chosen as primary end point. Genotyping of the -2849G/A, -1082G/A, -592C/A and +4259A/G polymorphisms of the IL-10 gene was performed by MassArray platform. After adjusting for clinical variables, three polymorphisms significantly increased the risk of restenosis (-2849AA: relative risk (RR), 1.7, 95% confidence interval (CI), 1.2-2.5; -1082AA: RR, 1.4, 95% CI, 1.1-1.8 and +4259GG: RR, 2.0, 95% CI, 1.4-2.8). To further exclude possible involvement of neighboring genes due to LD in the IL-10 locus, additional polymorphisms were genotyped. The results reveal that association of the IL-10 gene with restenosis is independent of flanking genes. Our findings demonstrate that IL-10 is associated with restenosis and therefore support the hypothesis that anti-inflammatory genes also may be involved in developing restenosis. Furthermore, they may provide a new targeting gene for drug-eluting stents.
Monraats
P S
PS
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Kurreeman
F A S
FA
Pons
D
D
Sewgobind
V D K D
VD
de Vries
F R
FR
Zwinderman
A H
AH
de Maat
M P M
MP
Doevendans
P A
PA
de Winter
R J
RJ
Tio
R A
RA
Waltenberger
J
J
Huizinga
T W J
TW
Eefting
D
D
Quax
P H A
PH
Frants
R R
RR
van der Laarse
A
A
van der Wall
E E
EE
Jukema
J W
JW
D020413:3' Untranslated Regions; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D023903:Coronary Restenosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D020413:3' Untranslated Regions; D016753:Interleukin-10