Plasminogen activator inhibitor-1 is associated with the metabolism and development of advanced colonic polyps

Tsung Hsing Chen, Chen Ming Hsu, Hung Chih Hsu, Cheng Tang Chiu, Ming Yao Su, Yin Yi Chu, Ming Ling Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

4 Scopus citations

Abstract

Implications of plasminogen activator inhibitor-1 (PAI-1) in colonic polyps remain elusive. A prospective study was conducted with 188 consecutive subjects who underwent colonoscopy at a tertiary referral center. Biochemical parameters, serum PAI-1 levels, PAI-1 single-nucleotide polymorphisms (rs-1799889), and colonic polyp profiles were analyzed at baseline and 24 and 48 weeks postpolypectomy. Of 188 patients (mean age: 56.8 years), 78.7% had adenomas; the median polyp number and size were 2 and 1.2 cm, respectively. Multivariate analyses revealed the following baseline associations: PAI-1 levels (95% confidence interval [CI] for estimated β: 0.012–0.223) and polyp pathology (0.294–0.63) with polyp size; polyp size (0.085–0.498) and platelet count (0.013–0.027) with PAI-1 levels. At 24 weeks postpolypectomy, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and platelet count were independently associated with PAI-1 levels. Among patients with colonic adenomas, baseline PAI-1 levels (95% CI odds ratio: 1.06–1.686; cut-off value: >10.65 ng/mL, area under curve: 0.662, P = 0.032) and the PAI-1-rs-1799889 4G/ 4G genotype (0.036–0.912) were associated with high-grade dysplasia. Compared with baseline levels, repeated measures analysis of variance showed that PAI-1 levels increased, with concurrent increased HOMA-IR indexes, but decreased alanine transaminase levels and polyp size in follow-up colonoscopies at 24 weeks postpolypectomy. PAI-1 returned to baseline levels, and HOMA-IRs and triglyceride/high-density lipoprotein-cholesterol ratios decreased at 48 weeks postpolypectomy. Taken together, serum PAI-1 levels were positively associated with colonic polyp size and high-grade dysplasia, which was modulated by the PAI-1-rs-1799889 4G/ 4G genotype. The beneficial postpolypectomy inflammatory and metabolic alterations might be transiently counter regulated by elevated PAI-1 levels, with a link to HOMA-IR.

Original languageEnglish
Pages (from-to)43-53
Number of pages11
JournalTranslational Research
Volume200
DOIs
StatePublished - 10 2018

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© 2018

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