Interaction between rs4073 IL-8 gene polymorphism, serum IL-8 and development of alcoholic hepatitis

Arisheva O.S.: Peoples' Friendship University of Russia

Ivanov A.S.: Peoples' Friendship University of Russia

Garmash I.V.: Peoples' Friendship University of Russia

Goreva L.A.: Peoples Friendship University of Russia (PFUR), Vinogradov City Clinical Hospital, Moscow, Russia

Markova M.A.: Peoples' Friendship University of Russia

Avdoshina S.V.: Peoples' Friendship University of Russia

Terebilina N.N.: National Scientific Research Centre on Addictions, V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Moscow

Pirozhkov S.V.: Sechenov First Moscow State Medical University, Moscow, Russia

Baronets V.Yu.: National Scientific Research Centre on Addictions, V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Moscow

Peregud D.I.: National Scientific Research Centre on Addictions, V.P. Serbsky National Medical Research Centre for Psychiatry and Narcology, Moscow

Kobalava Zh.D.: Peoples Friendship University of Russia (PFUR), Vinogradov City Clinical Hospital, Moscow, Russia

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Summary

Aim

To study the interrelations between the rs4073 polymorphism of the IL-8 gene, IL-8 serum levels and severity of alcoholic hepatitis (AH).

Material and methods

We enrolled 93 patients with AH (age 49.5±9.1 years, 77% males). The severity of AH was evaluated using the Maddray score discriminant function (MDF). Sixty six patients had mild AH (MDF 8.0±1.1), whereas 27 patients presented with severe AH (MDF 63.0±15.3). Twenty four alcohol abusers without liver disease formed the control group. Serum IL-8 levels were measured with ELISA. Real time PCR was used to determine the allelic variants of the rs4073 IL-8 gene.

Results

Serum IL-8 levels in patients with severe AH were significantly higher than in patients with mild AH and control patients. Severe AH was associated with the threshold IL-8 level >71.8 pg/ml with 62.5% sensitivity and 77.8% specificity. Multivariate correlation analysis showed no association between IL-8 levels and any clinical, laboratory or instrumental parameters in the studied groups. IL-8 rs4073 genotype ТТ and allele Т were more frequent in patients with mild and severe AH compared to genotype АА and allele А, respectively. Moreover, heavy drinkers carrying genotype ТТ and allele Т had significantly higher risk of AH compared to genotype AA and allele A carriers. Significant association was found between high serum IL-8 levels and carriage of the T allele and TT genotype among patients with severe AH.

Conclusion

Serum IL-8 concentration was increased in patients with severe AH and did not correlate with routine clinical or laboratory parameters. High IL-8 levels were associated with carriage of allele T and genotype TT of the rs4073 IL-8 gene in patients with severe AH. Genotype TT and T allele were more prevalent in AH and increased the risk of its development.

Key words

Alcoholic hepatitis, IL-8, rs473, IL-8 gene.