Lack of association of some chemokine system polymorphisms with the risks of death and hepatocellular carcinoma occurrence in patients with alcoholic cirrhosis: a prospective study.

Abstract

BACKGROUND:

Polymorphisms in genes encoding for the chemokines stromal cell-derived factor-1 (SDF-1)/CXCL12, monocyte chemotactic protein-1 (MCP-1)/CCL2, or for the chemokine receptors, CC chemokine receptor 5 (CCR5) or CC chemokine receptor 2 (CCR2) have been associated with the progression of hepatitis C virus-related liver injury and with various cancer development. Their influence on the prognosis of alcoholic liver disease is unknown.

PATIENTS AND METHODS:

SDF-1 3'A, MCP-1(-2518), CCR5-Delta32 and CCR2-64I polymorphisms, SDF-1alpha, regulated upon activation normal T cells expressed and secreted (RANTES)/CCL5 and MCP-1 sera levels were determined in 222 alcoholic patients, included at the time of cirrhosis diagnosis and prospectively followed up.

RESULTS:

Carriers and noncarriers of each genetic marker had similar baseline characteristics estimating the severity of liver disease. Mean time of follow-up of the cohort was 62.9+/-43.2 months. One hundred and forty-seven out of 222 (66.3%) patients were alive at the end of the study. The occurrence of death (75/222; 33.7%) or hepatocellular carcinoma (67/222; 30.1%) during follow-up was similar among carriers and noncarriers of each polymorphism. No association between the carriage of mutated alleles and chemokine sera levels was found: CCR5-Delta32/RANTES, SDF-1 3'A/SDF-1alpha and CCR2-64I or MCP-1(-2518)/MCP-1. Baseline RANTES, SDF-1alpha and MCP-1 sera levels were associated neither with the risk of death nor with the risk of hepatocellular carcinoma.

CONCLUSIONS:

The present study suggests the lack of association of SDF-1 3'A, MCP-1(-2518), CCR5-Delta32 and CCR2-64I polymorphisms with death and hepatocellular carcinoma occurrence in cirrhotic alcoholic patients.

• Authors: Pierre Nahon, Angela Sutton, Pierre Rufat, Charles Faisant, Chantal Simon, Nathalie Barget, Jean-Claude Trinchet, Michel Beaugrand, Liliane Gattegno, Nathalie Charnaux
• Journal: European journal of gastroenterology & hepatology (Eur J Gastroenterol Hepatol) Vol. 19 Issue 5 Pg. 425-31 (May 2007) ISSN: 0954-691X [Print] England
• PMID: 17413295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL2 protein, human
• CCR2 protein, human
• CXCL12 protein, human
• Chemokine CCL2
• Chemokine CCL5
• Chemokine CXCL12
• Chemokines
• Chemokines, CXC
• Receptors, CCR2
• Receptors, CCR5
• Receptors, Chemokine

Topics

• Adult
• Aged
• Alcohol Drinking
• Carcinoma, Hepatocellular (etiology, genetics)
• Chemokine CCL2 (blood, genetics)
• Chemokine CCL5 (blood)
• Chemokine CXCL12
• Chemokines (genetics)
• Chemokines, CXC (blood, genetics)
• Epidemiologic Methods
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Liver Cirrhosis, Alcoholic (blood, complications, genetics)
• Liver Neoplasms (etiology, genetics)
• Male
• Middle Aged
• Polymorphism, Genetic
• Prognosis
• Receptors, CCR2
• Receptors, CCR5 (genetics)
• Receptors, Chemokine (genetics)
• Temperance