Cholelithiasis in Patients with Gaucher Disease type 1: Risk Factors and the Role of ABCG5/ABCG8 Gene Variants

J Gastrointestin Liver Dis. 2016 Dec;25(4):447-455. doi: 10.15403/jgld.2014.1121.254.zim.


Background and aim: Patients with Gaucher disease type 1 (GD1) show an altered lipid profile and a certain degree of insulin resistance, which might contribute to cholelithiasis (CL) and could possibly be associated with ABCG5/ABCG8 gene variants. We aimed to investigate the prevalence of CL in Caucasian adult patients with GD1 and the possible risk factors, including gene variants of the ABCG5/ABCG8 genes.

Methods: 61 Caucasian patients with GD1 (38 female/23male), aged 18-62 years and 61 healthy subjects matched for age, gender and BMI, without CL, for comparison of lipid profiles. Data before start of enzyme replacement therapy (ERT) were recorded: clinical, haematological, severity parameters, splenectomy, genotype. Fasting lipid profiles before ERT, glycemia, insulinaemia, HOMA-IR at the last visit were documented. Genotyping for the gene variants D19H, Y54C, T400K, A632V (ABCG8); Q604E (ABCG5) was performed.

Results: CL occurred in 45.9% of patients. Risk factors were: age, family history of CL, higher BMI values, LDL-cholesterol (LDL-C), disease severity, splenectomy. A specific dyslipidemia was found in patients vs. controls. Total serum cholesterol (TC) and LDL-C were higher in patients with CL than in those without; no obvious influence of insulin-resistance to lithogenesis was found. Patients with the GG genotype of D19H and the CC genotype of T400K (ABCG8 gene) had significantly higher levels of TC and LDL-C.

Conclusion: Patients with GD1 showed an increased prevalence of CL, which was associated with common and disease-specific risk factors. Starting ERT soon after clinical onset and avoiding splenectomy might reduce the risk of CL in GD1.

Publication types

  • Observational Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 5 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 8 / genetics*
  • Adolescent
  • Adult
  • Case-Control Studies
  • Cholelithiasis / diagnosis
  • Cholelithiasis / epidemiology
  • Cholelithiasis / genetics*
  • Cross-Sectional Studies
  • Enzyme Replacement Therapy
  • European Continental Ancestry Group / genetics
  • Female
  • Gaucher Disease / diagnosis
  • Gaucher Disease / drug therapy
  • Gaucher Disease / epidemiology
  • Gaucher Disease / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Glucosylceramidase / therapeutic use
  • Heterozygote
  • Homozygote
  • Humans
  • Lipoproteins / genetics*
  • Male
  • Middle Aged
  • Phenotype
  • Prevalence
  • Risk Factors
  • Romania / epidemiology
  • Young Adult


  • ABCG5 protein, human
  • ABCG8 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 5
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • Lipoproteins
  • Glucosylceramidase