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

Authors

  • Anca Zimmermann 1st Clinic and Polyclinic of Internal Medicine, Dept. Endocrinology and Metabolic Diseases, University of Mainz, Mainz, Germany
  • Radu A Popp Dept. of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
  • Camelia Al-Khzouz Center of Genetic Diseases, Emergency Children’s Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
  • Simona Bucerzan Center of Genetic Diseases, Emergency Children’s Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
  • Ioana Naşcu Center of Genetic Diseases, Emergency Children’s Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
  • Daniel Leucuta Dept. of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
  • Peter R. Galle Clinic and Polyclinic of Internal Medicine, University of Mainz, Mainz, Germany
  • Paula Grigorescu-Sido Center of Genetic Diseases, Emergency Children’s Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania

DOI:

https://doi.org/10.15403/jgld.2014.1121.254.zim

Keywords:

cholelithiasis, Gaucher disease, ABCG5/ABCG8 gene variants

Abstract

Background & 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.

Abbreviations: ABC: ATP-binding cassette; CL: cholelithiasis; ERT: enzyme replacement therapy; GBA1: acid-beta-glucosidase gene; GD1: Gaucher disease type 1; HOMA-IR: homeostasis model-assessment insulin resistance; HDL-C: HDL-cholesterol; LDL-C: LDL-cholesterol; MN: multiples of normal; PCR-RFLP: polymerase chain reaction-restriction fragment length polymorphism; SSI: severity score index; TC: total cholesterol; TG: triglycerides.

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Published

2016-12-01

How to Cite

1.
Zimmermann A, Popp RA, Al-Khzouz C, Bucerzan S, Naşcu I, Leucuta D, Galle PR, Grigorescu-Sido P. Cholelithiasis in Patients with Gaucher Disease type 1: Risk Factors and the Role of ABCG5/ABCG8 Gene Variants. JGLD [Internet]. 2016 Dec. 1 [cited 2025 Dec. 5];25(4):447-55. Available from: https://jgld.ro/jgld/index.php/jgld/article/view/1030

Issue

Vol. 25 No. 4: December 2016

Section

Original Article