RT Book, Section
A1 Lammert, Marcin Krawczy and Frank
A2 Murray, Michael F.
A2 Babyatsky, Mark W.
A2 Giovanni, Monica A.
A2 Alkuraya, Fowzan S.
A2 Stewart, Douglas R.
SR Print(0)
ID 1102702360
T1 Gallstone Disease
T2 Clinical Genomics: Practical Applications in Adult Patient Care
YR 2014
FD 2014
PB McGraw-Hill Education
PP New York, NY
SN 9780071622448
LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102702360
RD 2024/04/25
AB Disease  summary:Gallstone  disease  is  a  complex  trait  resulting  from  an  interaction  between  genetic  predisposition  and  environmental  risk  factors.  In  patients  carrying  rare  monogenic  mutations  gallstones  develop  mostly  due  to  genetic  risk  factors.  On  the  other  hand,  in  carriers  of  common  risk  variants,  stones  form  predominantly  due  to  environmental  triggers  interacting  with  these  genetic  variants.Gallstone  disease  affects  10%  to  50%  of  adults  in  developed  countries;  prevalence  rates  of  gallstones  in  developing  countries  are  rising  constantly.  The  disease  is  rare  in  children.Gallstones  can  be  divided  into  three  subtypes:  cholesterol  gallstones,  which  are  most  common  (>95%)  and  compromise  predominantly  cholesterol,  pigment  gallstones  that  mainly  consist  of  calcium  bilirubinate,  and  mixed  stones.Nongenetic  risk  factors  include  age,  parity,  metabolic  syndrome,  obesity,  and  insulin  resistance.Most  patients  with  gallstones  remain  asymptomatic  throughout  their  lives;  biliary  colic  represents  the  most  common  sign  of  symptomatic  disease,  which  develops  in  20%  of  patients.In  symptomatic  patients  early  surgery  is  indicated  due  to  recurrence  of  symptoms  and  high  complication  rates.Differential  diagnosis:Abdominal  aneurysm,  acute  and  chronic  pancreatitis,  biliary  dyskinesia,  diverticulitis,  functional  gastrointestinal  disorders,  peptic  ulcer  diseaseMonogenic  forms:Monogenic  cholelithiasis  is  rare  but  the  presence  of  predisposing  variants  substantially  increases  the  risk  of  disease  and  the  recurrence  of  stones  after  treatment.  Bilirubin  gallstones  can  be  caused  by  single-gene  mutations  known  to  increase  the  risk  of  hemolytic  anemias,  in  particular  in  children  (hereditary  spherocytosis:  ANK1,  EPB42,  SLC4A1,  SPTA1,  SPTB;  sickle  cell  disease:  HBB;  thalassemia  major  and  intermedia:  HBB;  erythrocyte  enzyme  deficiencies:  AKI,  G6PD,  GPI,  GSR,  PGK1,  PKLR,  TPII).  Patients  with  risk  variants  of  ABCB4,  the  gene  encoding  the  hepatobiliary  phosphatidylcholine  floppase,  develop  the  so-called  low  phospholipid-associated  cholelithiasis  (LPAC)  syndrome.Family  history:Gallstone  disease  develops  up  to  five  times  more  frequently  in  family  members  of  affected  individuals.Twin  studies:Twin  studies  have  demonstrated  that  in  Europeans  the  genetic  risk  factors  account  for  approximately  25%  of  total  disease  risk.Environmental  factors:Environmental  effects  account  for  75%  of  gallstone  risk.Genome-wide  association  scans  (GWASs):To  date,  one  GWAS  on  gallstones  has  been  published.  The  analysis  of  280  cases  and  360  controls  in  the  screening  panel,  subsequently  replicated  in  1832  German  and  167  Chilean  patients,  identified  a  common  variant  of  the  hepatobiliary  cholesterol  transporter  (ABCG8  p.D19H)  as  the  first  common  genetic  risk  factor  for  gallstone  formation  in  humans.