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

6533b856fe1ef96bd12b1d06

RESEARCH PRODUCT

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

Ioana Naşcu Radu A. Popp Peter R. Galle Anca Zimmermann Simona Bucerzan Paula Grigorescu-sido Daniel Corneliu Leucuta Camelia Alkhzouz

subject

Adult Male 0301 basic medicine Heterozygote medicine.medical_specialty Adolescent Lipoproteins medicine.medical_treatment Splenectomy ABCG8 030105 genetics & heredity Gastroenterology White People Young Adult 03 medical and health sciences Insulin resistance Gene Frequency Cholelithiasis Risk Factors Internal medicine Genotype Prevalence medicine Humans Enzyme Replacement Therapy Genetic Predisposition to Disease ATP Binding Cassette Transporter Subfamily G Member 5 Genetic Association Studies Gaucher Disease medicine.diagnostic_test Romania business.industry ATP Binding Cassette Transporter Subfamily G Member 8 Homozygote Gastroenterology Case-control study Genetic Variation Enzyme replacement therapy Middle Aged medicine.disease Cross-Sectional Studies Phenotype Case-Control Studies Glucosylceramidase Female Lipid profile business Dyslipidemia

description

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.

year	journal	country	edition	language
2016-12-17	Journal of Gastrointestinal and Liver Diseases

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