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To test for an association with risk for restenosis after coronary stent placement, the TNF-alpha and IL-10 polymorphisms were analyzed by 5' exonuclease TaqMan assays in 162 patients who initially underwent coronary stenting. Analysis of basal and procedure coronary angiographies revealed a higher proportion of restenosis in lesions treated with bare metal stents compared with those treated with drug-eluting stents (P < 0.001). Distribution of TNF-alpha genotypes was similar in patients with and without restenosis. The IL-10 polymorphisms showed a moderate protective trend of the -819 TT genotype against restenosis when the lesions were analyzed (P = 0.071, OR = 0.471). Multivariate analysis confirmed a protective role for drug-eluting stents (P < 0.001, OR = 0.199) and the -819 TT genotype (P = 0.037, OR = 0.391). These results suggest the IL-10 -819 TT genotype has a protective role against in-stent restenosis.