[Association between plasminogen activator inhibitor 1 gene polymorphisms and the risk and clinical phenotypes of
1Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Abstract:
Objective: To investigate the association between plasminogen activator inhibitor 1 (PAI-1) gene polymorphisms and the risk and clinical phenotypes of Crohn's disease (CD). Methods: The CD patients (CD group) and healthy controls (control group) at the Second Affiliated Hospital of Wenzhou Medical University between January 2020 and January 2025 were retrospectively collected. Genotypes of PAI-1 gene at loci rs6092, rs7242 and rs2227631 were examined. The distribution differences of PAI-1 gene polymorphisms were compared between CD group and control group, as well as among CD patients with different clinical phenotypes [disease location (terminal ileal-type, colonic-type, ileocolic-type, and upper gastrointestinal-type), disease behavior (non-stricturing non-penetrating-type, stricturing-type, and penetrating-type)]. Multivariate logistic regression models were used to analyze the association between PAI-1 gene polymorphisms and the risk and clinical phenotypes of CD. Results: The CD group consisted of 311 participants [202 males and 109 females, aged (32.2±12.8) years], while the control group consisted of 495 participants [318 males and 177 females, aged (32.3±13.1) years]. The variant genotype (GA+AA) [23.2% (72/311) vs 15.6% (77/495), P=0.021]and variant allele (A) [11.9% (74/622) vs 8.0% (79/990), P=0.027]of rs6092 were more frequent in the CD group than those in the control group. The variant genotype (TG+GG) of rs7242 was less frequent than that of the control group [68.2% (212/311) vs 76.0% (376/495), P=0.045]. The variant genotype (GA+AA) of rs6092 (OR=1.53, 95%CI: 1.06-2.21) and the variant genotype (TG+GG) of rs7242 (OR=0.72, 95%CI: 0.52-0.99)were factors associated with the risk of developing CD. The variant genotype (TG+GG) [64.0% (146/228) vs 79.5% (66/83), P=0.030] and variant allele (G) [41.9% (191/456) vs 54.2% (90/166), P=0.018] of rs7242 in the patients with colonic-type and ileocolic-type CD were less frequent than those with terminal ileal-type CD. The variant genotype (TG+GG) (OR=0.45, 95%CI: 0.24-0.82) of rs7242 was a factor associated with the colonic involvement (the disease location is colonic-type or ileocolic-type) in CD patients. Conclusions: The variant genotype (GA+AA) of rs6092 is associated with an increased risk of CD. The variant genotype (TG+GG) of rs7242 is associated with a lower risk of developing CD and colonic involvement (the disease location is colonic-type or ileocolic-type).
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