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.
Zee
Robert Y L
RY
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. rzee@rics.bwh.harvard.edu
Cook
Nancy R
NR
Kim
Chung-Ah
CA
Fernandez-Cruz
Arturo
A
Lindpaintner
Klaus
K
D000368:Aged; D000483:Alleles; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D015331:Cohort Studies; D023903:Coronary Restenosis / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors