Sistema Gastrointestinal e Digestivo

Abstrato

MDR1 C3435T Polymorphism is a Susceptible Marker for the Late Onset Japanese UC

Sawasaki T, Nanjo S and Sugiyama T

Background: The multi-drug resistance 1 (MDR1) gene is reported to correlate with the function and the expression of P-glycoprotein (P-gp), and the carriers of MDR1 C3435T polymorphism are speculated to have an increased susceptibility to ulcerative colitis (UC) in western countries. The aim of this study is to investigate whether MDR1 C3435T polymorphism is a susceptible marker for the onset of UC in Japanese patients. Patients and Methods:We obtained blood samples from 38 patients with UC and that from 76 healthy controls, and genomic DNA from leucocytes was extracted. MDR1 C3435T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism methods. The expression of P-gp was examined by immunohistochemistry in colonic tissues with UC. Results: Both the frequencies of TT genotype (p=0.023) and T allele (p=0.011) were significantly higher in the late onset UC groups than in the control group in Japanese UC patients. The protein of P-gp in colonic tissues showed lower expression in UC patients with TT genotype by immunohistological analysis. Conclusion: MDR1 C3435T polymorphisms are linked to the susceptibility of the late onset Japanese UC patients, probably via the lower exported activity of the related pathogenic environmental factors in colon.