title: A functional polymorphism of the stromelysin gene (MMP-3) influences susceptibility to primary sclerosing cholangitis.
abstract: OBJECTIVE
  We have investigated the influence of a biallelic polymorphism of the promoter region of stromelysin (matrix metalloproteinase 3) on susceptibility to primary sclerosing cholangitis (PSC). The 5A allele is associated with increased transcription, compared with wild-type (6A).
  
  
  METHODS
  An allelic association study was performed: in stage 1, 52 PSC patients (43 with inflammatory bowel disease [IBD]) and 99 healthy subjects (HS) were genotyped. In stage 2, 59 PSC patients (49 IBD), 84 patients with uncomplicated ulcerative colitis, and 72 HS were genotyped.
  
  
  RESULTS
  In stage 1, 5A carriage rate (90.4% vs. 72.7%; P = 0.012) and 5A allelic frequency (65.4% vs. 48.5%; P = 0.005) were increased, and 6A homozygosity was reduced in PSC (9.6% vs. 27.3%; P = 0.012). In stage 2, 5A allelic carriage was increased in PSC (93.2% vs. 76.4% in HS; P = 0.0092) and 6A homozygosity was reduced (6.8% vs. 23.8% in HS; P = 0.0092). Portal hypertension was associated with 5A homozygosity in PSC (P = 0.035; odds ratio [OR], 3.88). In the combined data set, 5A allelic frequencies (63.5% vs. 49.4%; P = 0.001; OR, 1.78) and 5A carriage rates (91.9% vs. 74.2%; P = 0.0002; OR, 3.92) were increased, and 6A homozygosity was reduced in PSC (8.1% vs. 25.7%; P = 0.0002; OR, 0.25). Overall, portal hypertension was associated with 5A homozygosity (P = 0.0192; OR, 3.12).
  
  
  CONCLUSIONS
  Stromelysin polymorphism may influence susceptibility and disease progression in PSC.
authors: Oxford Radcliffe Hospitals, Oxford, England. j.satsangi@ed.ac.uk
authors: J
authors: J
authors: Satsangi
authors: R W
authors: RW
authors: Chapman
authors: N
authors: N
authors: Haldar
authors: P
authors: P
authors: Donaldson
authors: S
authors: S
authors: Mitchell
authors: J
authors: J
authors: Simmons
authors: S
authors: S
authors: Norris
authors: S E
authors: SE
authors: Marshall
authors: J I
authors: JI
authors: Bell
authors: D P
authors: DP
authors: Jewell
authors: K I
authors: KI
authors: Welsh
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D019278:Matrix Metalloproteinase 3