A functional polymorphism....

July 13, 2001

1: Gastroenterology 2001 Jul;121(1):124-30

A functional polymorphism of the stromelysin gene (mmp-3) influences

susceptibility to primary sclerosing cholangitis.

Satsangi J, Chapman RW, Haldar N, son P, S, J,

Norris S, Marshall SE, Bell JI, Jewell DP, Welsh KI.

Oxford Radcliffe Hospitals, Oxford, England.

Background & Aims: 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.

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