Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1

Yang, Xinling; Cullen, Susan N.; Li, Jin H.; Chapman, Roger W.; Jewell, D P

doi:10.1016/j.jhep.2003.11.009

Cited by 61 publications

(41 citation statements)

References 25 publications

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“…20,22,23 To the best of our knowledge, the present study is the first to demonstrate a significant association of the Lys56Met variant with reduced plasma sICAM1 concentrations. However, as noted by others, 20 the observed association of the variants tested with reduced plasma sICAM1 concentrations may be due to linkage disequilibrium with other (nonsynonymous or functional) genetic polymorphism(s) that affect sICAM1 concentrations.…”

Section: Discussionsupporting

confidence: 48%

Intercellular Adhesion Molecule 1 (ICAM1) Lys56Met and Gly241Arg Gene Variants, Plasma-Soluble ICAM1 Concentrations, and Risk of Incident Cardiovascular Events in 23 014 Initially Healthy White Women

Zee

Cheng

Erlich

et al. 2007

Stroke

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Background and Purpose-The objective of this study was to examine the association of 2 nonsynonymous intercellular adhesion molecule 1 (ICAM1) gene variants (Lys56Met and Gly241Arg) with baseline plasma soluble ICAM1 concentrations and with risk of total and selected cardiovascular disease (CVD) events in a prospective cohort of 23 014 apparently healthy white American women followed for 10 years. ICAM1 variations have been associated with plasma soluble ICAM1 concentrations and inflammatory conditions, including atherosclerosis. However, to date, no large prospective, genetic-epidemiological data set is available that would allow evaluation of the degree of association of these gene variants with risk of CVD. Methods-ICAM1 genotypes and baseline plasma soluble ICAM1 concentrations were determined. The primary outcome measure was a composite CVD end point (incident ischemic stroke, myocardial infarction, or death due to ischemic CVD); other measures were incident ischemic stroke, myocardial infarction, and coronary revascularization. During follow-up, 751 total incident CVD events, 187 incident myocardial infarction cases, 203 incident ischemic stroke cases, and 433 coronary revascularization events occurred. Results-All observed genotype frequencies were in Hardy-Weinberg equilibrium across the whole sample population. We found baseline plasma soluble ICAM1 concentrations to be significantly reduced among carriers of Met56 allele (PϽ0.0001) and Arg241 allele (PϽ0.0001) as compared with the respective noncarriers of these variants. However, the polymorphisms tested and the respective haplotypes were neither associated with overall risk nor with risk with risk for selected CVD events regardless of whether analyses were adjusted for traditional CVD risk factors/confounders (all P values Ͼ0.10). Conclusions-In this large prospective study, we found an association of the nonsynonymous gene variants tested with reduced baseline plasma soluble ICAM1 concentrations. However, no evidence was found for an association of the gene variants tested with the overall or selected CVD end points examined, suggesting that these variants may not add useful aids to current risk predictors for early assessment of cardiovascular events.

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Section: Discussionsupporting

confidence: 48%

Intercellular Adhesion Molecule 1 (ICAM1) Lys56Met and Gly241Arg Gene Variants, Plasma-Soluble ICAM1 Concentrations, and Risk of Incident Cardiovascular Events in 23 014 Initially Healthy White Women

Zee

Cheng

Erlich

et al. 2007

Stroke

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“…ICAM-1 is expressed on proliferating and interlobular bile ducts and elevated serum levels of soluble ICAMs have also been detected. Surprisingly, the E469E homozygote status for ICAM-1 was found to be associated with protection against PSC [21] . Studies regarding the immunogenetics of PSC were inconclusive in establishing a difference between East and West, due to a lack of extensive population based research.…”

Section: Immunogeneticsmentioning

confidence: 86%

Primary sclerosing cholangitis - What is the difference between east and west?

Shorbagi¹,

Bayraktar²

2008

WJG

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Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by inflammation and fibrotic obliteration of the hepatic biliary tree. It is commonly associated with inflammatory bowel disease (IBD). A number of complications can occur which require special consideration, the most important of which is the development of cholangiocellular carcinoma (CCC). Unfortunately, no medical therapy is currently available for the underlying liver disease. Liver transplantation is an effective, lifeextending option for patients with advanced PSC. Geographical variations between East and West include a second peak for age with a lower association with IBD in a Japanese population and female predominance in a lone study from Turkey. The clinical and biochemical Mayo criteria may not be universally applicable, as different patients show variations regarding the initial presentation and natural course of the disease. Directing research towards explaining these geographical differences and understanding the pathogenesis of PSC is required in order to develop better therapies for this devastating disease.

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“…ICAM-1 is expressed on proliferating bile ducts and interlobular bile ducts and when analyzed in patients for PSC, the E469E homozygote status for ICAM-1 is associated with protection against PSC [102]. Along a similar vein, the recent finding that MadCAM-1 and CCL25 are upregulated within the liver and not just restricted to the gastrointestinal tract helps explain why patients may develop PSC many years after a colectomy.…”

Section: Etiologymentioning

confidence: 93%

Primary Sclerosing Cholangitis

Enns¹

2006

Diseases of the Gallbladder and Bile Ducts

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Susceptibility to primary sclerosing cholangitis is associated with polymorphisms of intercellular adhesion molecule-1

Cited by 61 publications

References 25 publications

Intercellular Adhesion Molecule 1 (ICAM1) Lys56Met and Gly241Arg Gene Variants, Plasma-Soluble ICAM1 Concentrations, and Risk of Incident Cardiovascular Events in 23 014 Initially Healthy White Women

Intercellular Adhesion Molecule 1 (ICAM1) Lys56Met and Gly241Arg Gene Variants, Plasma-Soluble ICAM1 Concentrations, and Risk of Incident Cardiovascular Events in 23 014 Initially Healthy White Women

Primary sclerosing cholangitis - What is the difference between east and west?

Primary Sclerosing Cholangitis

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