title: Susceptibility to refractory ulcerative colitis is associated with polymorphism in the hMLH1 mismatch repair gene.
abstract: The hMLH1 gene lies in the linkage susceptibility region to inflammatory bowel disease (IBD) on 3p21. A single nucleotide polymorphism, 655A>G, in exon 8 of the gene causes an I219V change in the MLH1 protein. To test whether hMLH1 may confer susceptibility to ulcerative colitis (UC), we investigated an association between the 655A>G polymorphism and the disease. DNA-based technologies were used to analyze the 655A>G polymorphism in 201 UC patients and 126 healthy ethnically matched controls. The comparison of the allelic frequencies of the 655A>G polymorphism in UC patients and healthy controls did not show significant differences. However, genotype frequencies at the hMLH1 655 position were found to be significantly different when patients with and without refractory UC were compared. This was mainly attributable to a higher level of homozygosity for the G allele in refractory UC patients. Almost 5 times as many (4.9 times) refractory UC patients carried the GG genotype compared with nonrefractory patients (P < 0.0001). The present study provides evidence that the hMLH1 gene is involved in genetic susceptibility to refractory UC. If confirmed by other studies, the GG genotype at position 655 of the hMLH1 gene may represent a useful predictive factor for the clinical management of UC patients.
authors.affiliation: Gastroenterology Unit, Careggi Hospital, Florence, Italy.
authors.forename: Siro
authors.initials: S
authors.lastname: Bagnoli
authors.forename: Anna Laura
authors.initials: AL
authors.lastname: Putignano
authors.forename: German
authors.initials: G
authors.lastname: Melean
authors.forename: Silvana
authors.initials: S
authors.lastname: Baglioni
authors.forename: Roberta
authors.initials: R
authors.lastname: Sestini
authors.forename: Monica
authors.initials: M
authors.lastname: Milla
authors.forename: Giuseppe
authors.initials: G
authors.lastname: d'Albasio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Genuardi
authors.forename: Franco
authors.initials: F
authors.lastname: Pacini
authors.forename: Giacomo
authors.initials: G
authors.lastname: Trallori
authors.forename: Laura
authors.initials: L
authors.lastname: Papi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002352:Carrier Proteins; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012008:Recurrence; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1