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Article 6, 4/2016


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

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Anca Zimmermann1*, Radu A Popp2*, Camelia Al-Khzouz3, Simona Bucerzan3, Ioana Naşcu3, Daniel Leucuta4, Peter R. Galle5, Paula Grigorescu-Sido3

1)1st Clinic and Polyclinic of Internal Medicine, Dept. Endocrinology and Metabolic Diseases, University of Mainz, Mainz, Germany
2) Dept. of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
3) Center of Genetic Diseases, Emergency Children’s Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
4) Dept. of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania
5) Clinic and Polyclinic of Internal Medicine, University of Mainz, Mainz, Germany

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.254.zim

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.

Key words: cholelithiasis – Gaucher disease – ABCG5/ABCG8 gene variants.

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.