SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis

J Gastrointestin Liver Dis. 2019 Sep 12;28(3):297-302. doi: 10.15403/jgld-168.

Abstract

Background and aims: Two single nucleotide polymorphisms (SNPs) in SERPINA1 (Pi*Z rs28929474 and Pi*S rs17580) are risk factors for developing liver cirrhosis. A recent study identified a common SNP in HSD17B13 (rs72613567) that conferred protection from chronic liver disease. The aim of the present study was to test these associations in a cohort of Lithuanian patients with liver fibrosis or cirrhosis.

Methods: The study included 302 patients with cirrhosis, 127 patients with liver fibrosis (METAVIR stages I-III) and 548 controls, all from Lithuania. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Adjusted p value of ≤ 0.016 was considered significant.

Results: Genotype distributions of SERPINA1 and HSD17B13 SNPs were in Hardy-Weinberg equilibrium. SERPINA1 Pi*Z was not associated with liver fibrosis or cirrhosis. HSD17B13 rs10433937 (in high linkage disequilibrium with rs72613567; r 2 =0.96) also showed no overall association with liver disease, but the GG- genotype was associated with reduced risk of liver fibrosis (aOR 0.37, p=0.03). SERPINA1 Pi*S was associated with higher risk of developing hepatic fibrosis (aOR 3.42, p=0.001) and cirrhosis (aOR 2.59, p=0.02).

Conclusions: We found that SERPINA1 Pi*S variant conferred an increased risk of developing liver fibrosis, while SERPINA1 Pi*Z and HSD17B13 rs10433937 were not associated with liver fibrosis or cirrhosis of different aetiology.

MeSH terms

  • 17-Hydroxysteroid Dehydrogenases / genetics*
  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • alpha 1-Antitrypsin / genetics*

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin
  • 17-Hydroxysteroid Dehydrogenases
  • HSD17B13 protein, human