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

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.