Correlation of polymorphism in the interleukin-1 receptor antagonist gene intron 2 with alcoholic liver disease.

Background: Interleukin-1 receptor antagonist (IL-1ra) can inhibit the pro-inflammatory effects of IL-1, which recently has been thought to involve the pathogenesis of alcoholic liver disease (ALD). This study was undertaken to determine whether there is any association between IL-1ra gene polymorphism and ALD in a Chinese population.

Methods: The polymorphism of IL-1ra gene intron 2 (VNTR) was assessed in 165 alcoholics (43 alcohol-dependent subjects without liver diseases, 30 patients with alcoholic fatty liver, 61 patients with alcoholic hepatitis and 31 patients with alcoholic cirrhosis) and 65 healthy control subjects by PCR with DNA of peripheral blood mononuclear cells.

Results: The rate of IL-1RN*1 carriage was statistically higher in the alcoholics than in the control group (98.79% vs 93.85%, chi2=4.48, P<0.050). And the IL-1RN*1 allele frequency was more common in the alcoholics than in the control group (86.67% vs 76.92%, chi2=6.56, P<0.025). IL-1RN*1 heterozygote was significantly more frequent in the patients with alcoholic hepatitis or those with cirrhosis than in the alcohol-dependent subjects without liver diseases (32.79%, 29.03% vs 9.30%; chi2=7.84, chi2=4.84; P<0.010, P<0.050). The IL-1RN*2 allele frequency in the patients with alcoholic hepatitis and the patients with cirrhosis was also significantly higher than in those alcoholics without liver diseases (13.93%, 17.74% vs 4.65%; chi2=4.79, chi2=6.78; P<0.050, P<0.010). But the frequencies of IL-1RN*1 heterozygote and IL-1RN*2 allele appear to be not different between the patients with alcoholic fatty liver and the alcoholics without liver diseases.

Conclusions: IL-1ra gene polymorphism is closely associated with race. IL-1RN*2 allele doesn't influence the susceptibility to ALD, but the gene carriers with ALD have additional risk for aggravation of the illness.