Relationship between BDNF gene polymorphisms and alcohol-related liver cirrhosis

Abstract

Abstract Background and aim Brain-derived neurotrophic factor (BDNF) functions not only in the brain but also in peripheral tissues such as the liver. Genetic factors determine the development of alcohol dependence and somatic consequences of chronic intoxication, especially liver cirrhosis. The BDNF gene polymorphisms are associated with alcohol dependence; however, their relationship with the development of alcohol-related liver cirrhosis (ALC) has not yet been established. This study evaluated the association between single-nucleotide polymorphisms (SNPs) within the BDNF gene and liver cirrhosis in heavy drinkers. Methods BDNF-related SNPs rs925946, rs6265, rs10835210, rs7103411, and rs75945125 were determined using real-time PCR in heavy drinkers with and without liver cirrhosis. Single SNPs and defined haplotypes within the BDNF gene were tested for association with ALC. Results According to both codominant and recessive genetic models, carriers of the rs925946 TT genotype have an elevated risk of liver cirrhosis development with odds ratios (confidence intervals) 6.287 (1.286–30.738) and 6.321 (1.317–30.348), respectively. BDNF SNPs rs6265, rs10835210, rs7103411, and rs75945125 do not associate with risk of ALC. One block of haplotypes consisting of rs10835210 and rs7103411 demonstrated linkage disequilibrium (D′ = 1 and r 2 = 0.228). The revealed haplotypes do not associate with the development of liver cirrhosis in alcohol heavy drinkers. Conclusion Thus, the BDNF rs925946 SNP is associated with the risk of ALC in heavy drinkers. Future investigations of the BDNF gene-related genetic markers of ALC will help to objectively assess the risk and severity of liver damage and correct the corresponding therapy.

Keywords

• Alcohol use disorder
• Alcohol-related liver cirrhosis
• Genetic polymorphisms
• BDNF