The -159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers.
BACKGROUND
Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single-nucleotide polymorphism (-159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharide receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/-159C/T polymorphism and advanced ALD and acute-phase protein levels in heavy drinkers.


METHODS
A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/-159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), C-reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n = 35) were classified as having advanced ALD.


RESULTS
After adjusting for potential confounding variables, the CD14/-159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95% confidence interval, 1.09-8.24, p = 0.03) and serum LBP (p = 0.01) and sCD14 (p = 0.04) levels. The CD14/-159C/T polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM.


CONCLUSIONS
Our results support the notion that CD14/-159TT homozygous heavy drinkers have higher levels of the LPS-binding acute-phase proteins (LBP and sCD14) than do carriers of the CD14/-159C allele. Also, the CD14/-159TT genotype may be a risk factor for advanced ALD.
Campos
Joaquin
J
Department of Internal Medicine, Hospital Clinico Universitario, Fundación Publica Gallega de Medicina Genomica, Santiago de Compostela, Spain.
Gonzalez-Quintela
Arturo
A
Quinteiro
Celsa
C
Gude
Francisco
F
Perez
Luis-Fernando
LF
Torre
Jose-Antonio
JA
Vidal
Carmen
C
D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood*; D005260:Female; D006501:Hepatic Encephalopathy / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000097:blood*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008111:Liver Function Tests; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013030:Spain; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002097:C-Reactive Protein; D002352:Carrier Proteins; D007136:Immunoglobulins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D000099231:Lipopolysaccharide-Binding Protein