Cytokine gene polymorphisms in heavy drinkers with and without decompensated liver disease: a case-control study.
BACKGROUND
Twin studies have suggested some genetic predisposition to alcoholic liver disease (ALD). Cytokines may be involved in ALD pathogenesis. Several cytokine genes contain functionally significant polymorphisms. Associations between ALD and polymorphisms on the interleukin-1 (IL-1), IL-10, and tumor necrosis factor-alpha (TNF-alpha) genes have been reported but not confirmed.


OBJECTIVE
Comparison of allelic frequencies of cytokine gene polymorphisms between 223 patients with decompensated ALD (a more severe phenotype than in previous studies) and 162 controls with similar lifetime alcohol consumption but without serious liver disease.


METHODS
Genotyping of polymorphisms of the genes for IL-1A (+4,845), IL-1B (+3,954 and -511), IL-1 receptor antagonist (+2,018), IL-6 (-174), IL-10 (-574 and -1,117), and TNF-alpha (-238 and -308).


RESULTS
There were increases with respect to IL-6 -174 (2 x 3 chi(2)P < 0.1, OR for G allele carriage 1.61[1.05-2.48]) and Il-10 -592 (2 x 3 chi(2) 7.90, P < 0.01, OR for AA genotype carriage 4.85[1.40-16.8]) polymorphisms in patients compared with heavy-drinking controls. Differences were greater with analysis confined to Child's C patients. Genotype distribution for the other seven polymorphisms did not differ significantly between patients and heavy-drinking controls.


CONCLUSIONS
These data are consistent with a modest role for IL-6 -174, and IL-10 -592 polymorphisms in genetic susceptibility to ALD.
Gleeson
Dermot
D
Liver Unit Sheffield Teaching Hospitals, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Bradley
Martin P
MP
Jones
Jayne
J
Peck
Robert J
RJ
Bond
Sarah K
SK
Teare
M Dawn
MD
Duff
Gordon W
GW
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects*; D016022:Case-Control Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D016207:Cytokines; D015850:Interleukin-6; D016753:Interleukin-10