title: Cholelithiasis in Patients with Gaucher Disease type 1: Risk Factors and the Role of ABCG5/ABCG8 Gene Variants.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 1st Clinic and Polyclinic of Internal Medicine, Dept. Endocrinology and Metabolic Diseases, University of Mainz, Mainz, Germany. zimmeran@uni-mainz.de.
authors.forename: Anca
authors.initials: A
authors.lastname: Zimmermann
authors.affiliation: Dept. of Medical Genetics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Radu A
authors.initials: RA
authors.lastname: Popp
authors.affiliation: Center of Genetic Diseases, Emergency Children's Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Camelia
authors.initials: C
authors.lastname: Al-Khzouz
authors.affiliation: Center of Genetic Diseases, Emergency Children's Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Bucerzan
authors.affiliation: Center of Genetic Diseases, Emergency Children's Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Naşcu
authors.affiliation: Dept. of Medical Informatics and Biostatistics, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Daniel
authors.initials: D
authors.lastname: Leucuta
authors.affiliation: Clinic and Polyclinic of Internal Medicine, University of Mainz, Mainz, Germany.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.affiliation: Center of Genetic Diseases, Emergency Children's Hospital, Iuliu Hatieganu University of Medicine and Pharmacy Cluj, Cluj-Napoca, Romania.
authors.forename: Paula
authors.initials: P
authors.lastname: Grigorescu-Sido
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5 / Q000235:genetics*; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002769:Cholelithiasis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005962:Glucosylceramidase / Q000627:therapeutic use; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008074:Lipoproteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D012383:Romania / Q000453:epidemiology; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D008074:Lipoproteins; D005962:Glucosylceramidase