Z Gastroenterol 2016; 54 - KV331
DOI: 10.1055/s-0036-1587107

Frequent polymorphism p.D19 H of the biliary cholesterol transporter ABCG5/8 increases the risk of gallstone disease in children

M Krawczyk 1, 2, O Niewiadomska 3, I Jankowska 3, K Jankowski 4, J Gozdowska 5, D Lebensztejn 6, S Wiecek 7, F Lammert 1, P Socha 3
  • 1Saarland University Hospital, Department of Medicine II, Homburg, Deutschland
  • 2Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Polen
  • 3Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children's Memorial Health Institute, Warsaw, Polen
  • 4Deptartment Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Polen
  • 5Deptartment Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Polen
  • 6Department of Pediatrics, Gastroenterology and Allergology, Medical University of Bialystok, Bialystok, Polen
  • 7Department of Pediatrics, Silesian Medical Academy, Katowice, Polen

Introduction: Genetic studies demonstrated that gallstones in adults are frequent in carriers of the p.D19 H variant in the hepatobiliary cholesterol transporter ABCG5/8. Presence of the Gilbert polymorphism in the UGT1A1 gene further increases this risk. The genetic background of common lithiasis in children has yet to be defined. Hence we investigated the role of the ABCG8 and UGT1A1*28 variants in the development of gallstones in paediatric patients.

Materials and methods: In total 214 children with gallstone disease (age at diagnosis 1 month – 17 years, 107 males) were recruited. Children with history of total parenteral nutrition were excluded. Symptomatic stones were present in 138 children, 47 underwent cholecystectomy, and ERCP was required in 10 cases. Overall, 126 children received therapy with ursodeoxycholic acid (UDCA). The control cohort was composed of 172 adults (age 40 – 92 years, 70 males) with gallstones excluded by abdominal ultrasound. The ABCG8 p.D19 H and UGT1A1*28 variants were genotyped using TaqMan assays.

Results: The ABCG8 risk allele was more frequent in children with gallstones (14.9%, 2 homozygotes and 30 heterozygotes) than in controls (7.5%, 1 homozygote, 12 heterozygotes). Presence of the lithogenic genotype was associated with gallstone risk (common OR = 1.82, P = 0.03). Notably, even carriers of a single lithogenic allele demonstrated increased gallstone prevalence (OR = 2.18, 95%CI 1.08 – 4.40, P = 0.02). The population attributable risk was 3.7% of the total gallstone risk in children. On the other hand, the presence of this variant did not affect the decrease of stone size under therapy with UDCA and was not associated with symptoms (all P > 0.05). The UGT1A1*28 variant was neither associated with increased prevalence of gallstone disease in the entire cohort (P = 0.20) nor in separate analyses of males or females (both P > 0.05).

Discussion: Here we report for the first time that carriers of the ABCG8 p.D19 H variant are at increased risk of developing gallstones already at young age. Our results point to the presence of a common lithogenic pathway in adults and in children, for which future precise therapeutic strategies might be foreseen.