Combined polymorphisms of tumour necrosis factor alpha and interleukin-10 genes in patients with alcoholic hepatitis.

ABSTRACT

OBJECTIVES: The development and progression of alcoholic hepatitis are controlled by an extensive cytokine network which involves pro-inflammatory and anti-inflammatory cytokines. Genetic variations determining production of these cytokines have been described and the susceptibility to the disease may be determined by an imbalance in the expression of several candidate genes. METHODS: We have studied biallelic single nucleotide polymorphisms at positions (-308) and (-238) in the promoter region of the pro-inflammatory tumour necrosis factor alpha (TNF-alpha) and at positions (-1,082) and (-592) in the promoter of anti-inflammatory interleukin-10 (IL-10) in 134 patients with severe biopsy-proven alcoholic hepatitis and 145 healthy subjects. RESULTS: The frequency distribution of isolated cytokine genotypes did not differ between the two groups. The combination of at least one A or A allele for TNF-alpha, associated with a TNF-alpha high-producer phenotype, and one A or A allele for IL-10, associated with an IL-10 low-producer phenotype, was less frequent in patients (20.9 vs 33.8%, P=0.016, OR (95% CI)=0.52 (0.30-0.89)). The same combination in patients was associated with a higher risk of septic complications (32.5 vs 16.0%, P=0.031, OR (95% CI)=1.79 (1.07-6.00)) but not with in-hospital mortality. CONCLUSIONS: We have not found any relationship between the isolated polymorphisms and the risk of alcoholic hepatitis. Moreover, the imbalance between the pro-inflammatory and anti-inflammatory responses leading to high TNF-alpha production and low IL-10 was uncommon in alcoholic hepatitis. However, patients with this particular genotype appeared more susceptible to severe septic complications.