Susceptibility to refractory ulcerative colitis is associated with polymorphism in the hMLH1 mismatch repair gene

被引:21
作者
Bagnoli, S
Putignano, AL
Melean, G
Baglioni, S
Sestini, R
Milla, M
d'Albasio, G
Genuardi, M
Pacini, F
Trallori, G
Papi, L
机构
[1] Univ Florence, Med Genet Unit, Dept Clin Physiopathol, I-50134 Florence, Italy
[2] Careggi Hosp, Gastroenterol Unit, Florence, Italy
关键词
genetics; hMLH1; inflammatory bowel disease; refractory ulcerative colitis;
D O I
10.1097/00054725-200411000-00001
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 1219V 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.
引用
收藏
页码:705 / 708
页数:4
相关论文
共 21 条
  • [1] Association of Crohn's disease and ulcerative colitis with haplotypes of the MLH1 gene in Italian inflammatory bowel disease patients
    Annese, V
    Piepoli, A
    Andriulli, A
    Latiano, A
    Napolitano, G
    Li, HH
    Forabosco, P
    Devoto, M
    [J]. JOURNAL OF MEDICAL GENETICS, 2002, 39 (05) : 332 - 334
  • [2] Brentnall TA, 1996, CANCER RES, V56, P1237
  • [3] BUDOWLE B, 1991, AM J HUM GENET, V48, P137
  • [4] The CC chemokine receptor 5 Δ32 mutation is not associated with inflammatory bowel disease (IBD) in NE England
    Craggs, A
    Welfare, M
    Donaldson, PT
    Mansfield, JC
    [J]. GENES AND IMMUNITY, 2001, 2 (02) : 114 - 116
  • [5] Fleisher AS, 2000, CANCER RES, V60, P4864
  • [6] The interaction of the human MutL homologues in hereditary nonpolyposis colon cancer
    Guerrette, S
    Acharya, S
    Fishel, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) : 6336 - 6341
  • [7] Fine mapping of the chromosome 3p susceptibility locus in inflammatory bowel disease
    Hampe, J
    Lynch, NJ
    Daniels, S
    Bridger, S
    Macpherson, AJS
    Stokkers, P
    Forbes, A
    Lennard-Jones, JE
    Mathew, CG
    Curran, ME
    Schreiber, S
    [J]. GUT, 2001, 48 (02) : 191 - 197
  • [8] Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis
    Ishitsuka, T
    Kashiwagi, H
    Konishi, F
    [J]. JOURNAL OF CLINICAL PATHOLOGY, 2001, 54 (07) : 526 - 532
  • [9] KIM HG, 1994, AM J PATHOL, V145, P148
  • [10] Δ32 mutation of the chemokine-receptor 5 gene in inflammatory bowel disease
    Martin, K
    Heinzlmann, M
    Borchers, R
    Mack, M
    Loeschke, K
    Folwaczny, C
    [J]. CLINICAL IMMUNOLOGY, 2001, 98 (01) : 18 - 22