PNPLA3 rs738409 associates with alcoholic liver cirrhosis but not with serum levels of IL6, IL10, IL8 or CCL2 in the Russian population

Abstract

Introduction and aim: Polymorphic variant rs738409 within the PNPLA3 gene associates with alcoholic liver cirrhosis (ALC) in heavy drinkers of various ancestry but has not yet been established in the Russian population characterized by high incidence of ALC. PNPLA3 rs738409 involvement in the inflammatory process has been proposed as one of the mechanisms of liver dysfunction. Relationship between the PNPLA3 polymorphism and the biochemical markers of inflammation in patients with ALC remains unclear. The current study revealed the association between the rs738409 polymorphism, liver cirrhosis and serum cytokines in heavy drinkers in the Russian population. Materials and methods: The serum levels of IL6, IL10, IL8, and CCL2 along with PNPLA3 rs738409 polymorphism were determined in heavy drinkers (AA, n = 71) and heavy drinkers with diagnosed liver cirrhosis (ALC, n = 110). All of the recruited individuals were Caucasians and belonged to the Russian population. Results: Heavy drinkers carrying PNPLA3 rs738409 CG or CG+GG genotypes as compared with CC genotype carriers or G allele as compared with C allele carriers had significant risk of ALC. In ALC levels of interleukins and CCL2 increased as compared with AA. PNPLA3 rs738409 CC carriers had lower cirrhosis stage as compared with CG+GG carriers, however there were no differences of IL6, IL10, IL8 or CCL2 levels between G allele carriers and non-carriers in heavy drinkers. Conclusion: Thus, in the Russian population heavy drinkers carrying PNPLA3 rs738409 G allele are at higher risk of ALC, however the presence of rs738409 allele does not influence the serum cytokine levels.

Keywords

• Alcohol abuse
• Alcoholic liver cirrhosis
• Cytokines
• SNP
• PNPLA3