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.
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.


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.
Nahon
Pierre
P
UPRES EA 3410, UFR SMBH, Paris 13 University, Bobigny, France. pierre.nahon@jvr.ap-hop-paris.fr
Sutton
Angela
A
Rufat
Pierre
P
Faisant
Charles
C
Simon
Chantal
C
Barget
Nathalie
N
Trinchet
Jean-Claude
JC
Beaugrand
Michel
M
Gattegno
Liliane
L
Charnaux
Nathalie
N
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D018946:Chemokine CCL5 / Q000097:blood; D054377:Chemokine CXCL12; D018925:Chemokines / Q000235:genetics*; D019743:Chemokines, CXC / Q000097:blood / Q000235:genetics; D004812:Epidemiologic Methods; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000150:complications / Q000235:genetics*; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics; D013695:Temperance
C111835:CCL2 protein, human; C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine