TP53 haplotype-based analysis and incidence of post-angioplasty restenosis

The tumor suppressor gene product, in particular tumor suppressor protein p53 (TP53), has been suggested to play a role in post-angioplasty restenosis. However, no genetic-epidemiological studies relating to TP53 gene polymorphism(s) and the incidence of post-angioplasty restenosis are available. TP53 11951_11966dup16bp, R72P, and 13494G>A polymorphisms were characterized in a cohort of 779 patients, of whom 342 cases had developed restenosis (as defined by >50% loss of lumen compared with immediate post-procedure results) at repeat quantitative coronary angiography at six months post angioplasty. The haplotype-frequency distribution was marginally different between cases and controls with restenosis risk (chi(2)(7df)=13.08, P=0.070). Multivariable haplotype-based logistic regression indicated that haplotypes 16bp(-) -P72-G13494 [corrected], and 16bp(+) -P72-A13494 [corrected] exhibit protective effects on restenosis risk (odds ratio=0.58, 95%CI=0.40-0.83, P=0.0033; odds ratio=0.69, 95%CI=0.48-0.99, P=0.049, respectively). Multivariable haplotype-based linear regression again showed similar, significant association with degree of lumen loss. The present findings indicate protective effects of TP53 16bp(-) -P72-G13494 [corrected], and 16bp(+) -P72-A13494 [corrected] haplotypes in the incidence of restenosis after angioplasty. Furthermore, our study demonstrates that a haplotype-based approach can be more informative than a single-marker or marker-by-marker analysis.