A functional polymorphism of the NFKB1 gene increases the risk for alcoholic liver cirrhosis in patients with alcohol dependence

Alcohol Clin Exp Res. 2009 Nov;33(11):1857-62. doi: 10.1111/j.1530-0277.2009.01023.x. Epub 2009 Aug 10.

Abstract

Background: The genetic basis for the predisposition to alcoholic liver cirrhosis (ALC) remains unknown. Increasing evidence supports a role for the nuclear factor (NF)-kappaB, the NF-kappaB inhibitor alpha (NFKBIA), and the peroxisome proliferator-activated receptor (PPAR)-gamma in the pathogenesis of alcoholic liver disease, raising the possibility that common polymorphisms in genes encoding these molecules may confer susceptibility to ALC. The objective of this study was to analyze the relationship between common polymorphisms in NFKB1, NFKBIA, and PPARG2 genes and the presence of ALC.

Methods: A total of 258 male alcoholics (161 without liver disease and 97 with ALC) and 101 healthy controls were genotyped for the -94ins/delATTG NFKB1, 3'-UTR+126G>A NFKBIA, and 34C>G PPARG2 polymorphisms. The association of these genetic variants with ALC was tested in alcoholic patients with alcohol abuse and alcohol dependence. A logistic regression analysis was further performed to analyze the model of inheritance.

Results: We found an association between the presence of the deletion allele in NFKB1 polymorphism and ALC in patients with alcohol dependence. We found no association between NFKBIA and PPARG2 polymorphisms and the presence of ALC.

Conclusions: The deletion allele of the -94ins/del NFKB1 polymorphism could be associated with a higher risk of developing ALC through an increase in inflammation, as supported by previous data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcoholism / complications*
  • Alcoholism / genetics*
  • DNA / genetics
  • Female
  • Genotype
  • Humans
  • Liver Cirrhosis, Alcoholic / epidemiology*
  • Liver Cirrhosis, Alcoholic / genetics*
  • Logistic Models
  • Male
  • Middle Aged
  • NF-kappa B p50 Subunit / genetics*
  • Polymorphism, Genetic / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk
  • Young Adult

Substances

  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • DNA