A Functional Polymorphism of the Stromelysin Gene (MMP-3) Influences Susceptibility to Primary Sclerosing Cholangitis

Satsangi, Jack; Chapman, Roger W.; Haldar, Neil A.; Donaldson, Peter; Mitchell, Stephen; Simmons, Jonathan; Norris, Suzanne; Marshall, Sara E.; Bell, John I.; Welsh, Ken I.

doi:10.1053/gast.2001.25527

Cited by 90 publications

(55 citation statements)

References 17 publications

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“…Interestingly, a non-significant trend towards a higher frequency of the DRB1*1501 allele was noted among the patients with PSC and concurrent IBD compared with PSC patients without IBD, and the possibility should be held open that this HLA haplotype may harbour genetic variants of particular importance for the IBD phenotype in PSC. A similar notion can be made with regard to the MMP3 5A allele association detected by Satsangi et al [79] . Although the replication study by Wiencke et al [78] failed to confirm an overall association with PSC susceptibility, a significant association was evident when PSC patients with UC were compared with UC patients without liver disease.…”

Section: Genetic Associations With Clinical Subsets Of Psc Patientssupporting

confidence: 75%

Genetic epidemiology of primary sclerosing cholangitis

Karlsen

Schrumpf²,

Boberg³

2007

WJG

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The aetiology of primary sclerosing cholangitis (PSC) is not known. A more than 80-fold increased risk of PSC among first-degree relatives emphasizes the importance of genetic factors. Genetic associations within the human leukocyte antigen (HLA) complex on chromosome 6p21 were detected in PSC 25 years ago. Subsequent studies have substantiated beyond doubt that one or more genetic variants located within this genetic region are important. The true identities of these variants, however, remain to be identified. Several candidate genes at other chromosomal loci have also been investigated. However, according to strict criteria for what may be denominated a susceptibility gene in complex diseases, no such gene exists for PSC today. This review summarises present knowledge on the genetic susceptibility to PSC, as well as genetic associations with disease progression and clinical subsets of particular interest (inflammatory bowel disease and cholangiocarcinoma).

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Section: Genetic Associations With Clinical Subsets Of Psc Patientssupporting

confidence: 75%

Genetic epidemiology of primary sclerosing cholangitis

Karlsen

Schrumpf²,

Boberg³

2007

WJG

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“…12,13 This study provides evidence for an association between PSC and the chemokine receptor family, with a significantly increased frequency of CCR5-D32 heterozygotes (P ¼ 0.003) and a significantly higher CCR5-D32 allele frequency (P ¼ 0.007) in PSC patients compared to matched controls. CCR5-D32 was also significantly commoner in PSC compared to a large, unselected series of patients with IBD alone (P ¼ 0.027).…”

Section: Discussionmentioning

confidence: 62%

“…Interest in the genetics of PSC has been recently rekindled by two association analyses investigating the relevance of the TNF-a and stromolysin genes in the development of this disease. 12,13 While the association with the TNF2 allele was considered secondary to the known association with the A1-B8-DRB1*0301-DQA1*0501-DQB1*0201 haplotype, the association with the stromolysin gene was thought to be an independent one that may also influence disease progression. However, the patients in this second study were not HLA typed.…”

Section: Introductionmentioning

confidence: 99%

“…However, the patients in this second study were not HLA typed. 13 Recent interest in immunoregulatory genes has also focused on the chemokine family that are intimately involved in leucocyte trafficking and recruitment, and therefore are likely to play a crucial role in determining which cells migrate to the injured and/or inflamed bowel and liver. 14,15 Colonic epithelium shows upregulation of RANTES (regulated upon activation normal T-cell expressed and secreted), which is the natural ligand for the chemokine receptor CCR5.…”

Section: Introductionmentioning

confidence: 99%

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CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis

et al. 2004

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“…In this promoter polymorphism, Okamoto et al [29] reported that among HCV-LC patients, 5A carriers were diagnosed with liver cirrhosis at an earlier age (P = 0.017), and had higher Child-Pugh scores (P = 0.023) compared with 6A homozygotes. Satsangi et al [30] also found a higher 5A allele frequency among patients with advanced primary biliary cirrhosis.…”

Section: Discussionmentioning

confidence: 89%

Matrix Metalloproteinase (MMP)-3 Polymorphism in Patients with HBV Related Chronic Liver Disease

et al. 2007

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A common and important problem in patients with chronic hepatitis B is the progression of liver fibrosis. Matrix metalloproteinases (MMPs) play an important role in the progression of liver fibrosis. Our aim of this study was to examine the association of MMP-3 polymorphism with liver cirrhosis in Korean patients with chronic hepatitis B. Genomic DNA was extracted from 127 patients with chronic hepatitis B (CHB), 92 patients with hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC), and 146 healthy subjects. MMP-3 polymorphism was determined by polymerase-chain reaction-based assays, and the association with the progression of liver cirrhosis was investigated. With regard to MMP-3 polymorphism, there was no statistical difference in genotype distributions among the three groups. However, the peripheral platelet count of the 5A carriers was significantly lower than that of the 6A homozygotes in the HBV-LV group (85.0 +/- 36.9 vs. 109.8 +/- 47.0 x 10(9)/l; P = 0.02). With MMP-3 promoter polymorphism (rs3025058), a lower peripheral blood platelet count, which was related to advanced liver cirrhosis, was observed in 5A carriers. Therefore, more studies of MMP-3 gene polymorphism with larger populations should be conducted to further understand its role in the progression of liver cirrhosis.

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A Functional Polymorphism of the Stromelysin Gene (MMP-3) Influences Susceptibility to Primary Sclerosing Cholangitis

Cited by 90 publications

References 17 publications

Genetic epidemiology of primary sclerosing cholangitis

Genetic epidemiology of primary sclerosing cholangitis

CCR5-Δ32 mutation is strongly associated with primary sclerosing cholangitis

Matrix Metalloproteinase (MMP)-3 Polymorphism in Patients with HBV Related Chronic Liver Disease

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