title: Polymorphisms inUGT1A1Gene Predispose South Indians to Pigmentous Gallstones.
abstract: OBJECTIVE
  Pigmentous gallstones occur in South Indians despite significant higher levels of circulating cholesterol. This study was conducted to identify the biochemical and/or genetic causes for the formation of pigmentous gallstones in this ethnic group.
  
  
  METHODS
  Plasma lipid profile, bile cholesterol, acids, and phospholipid levels were estimated in patients with gall stone disease and age, sex matched controls using standard protocols. Twenty-seven SNPs related to cholesterol and bilirubin metabolism pathway genes were genotyped in the study population using the Sequenom platform. An equilibrium phase diagram involving bile salt-phospholipid-cholesterol was generated to relate phenotype with the genotype.
  
  
  RESULTS
  There were no significant differences in the lipid profiles between the patients (n= 305) and controls (n= 177). Biliary cholesterol, acids, and phospholipids were significantly different between patients and controls. Single locus analysis revealed association of variants inABCG6, ABCG8, andUGT1A1genes with the disease; however when correction was applied as multiple testing was done, only one variant (rs6742078) inUGT1A1gene was found to be associated with gall stone disease. Equilibrium phase diagram suggested that few samples were in the crystal formation zone. The mutant, but not wild type or heterozygous genotype of SNPs (rs6742078 and rs887829) inUGT1A1gene, was associated with significantly higher levels of bilirubin.
  
  
  CONCLUSIONS
  Higher incidence of pigment stones in South Indians could be due to raised serum bilirubin levels that may be ascribed to variant in theUGT1A1gene involved in glucuronidation of free bilirubin.
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Vishnubhotla Venkata
authors.initials: VV
authors.lastname: Ravikanth
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Guduru Venkat
authors.initials: GV
authors.lastname: Rao
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Bale
authors.initials: B
authors.lastname: Govardhan
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Mitnala
authors.initials: M
authors.lastname: Sasikala
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Chivukula
authors.initials: C
authors.lastname: Subramanyam
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: H V
authors.initials: HV
authors.lastname: Vivekananda Murthy
authors.affiliation: Asian Healthcare Foundation, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Siddapuram
authors.initials: S
authors.lastname: Siva Prasad
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: G
authors.initials: G
authors.lastname: Deepika
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Rebala
authors.initials: R
authors.lastname: Pradeep
authors.affiliation: Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082 Telangana, India.
authors.forename: Duvvuru
authors.initials: D
authors.lastname: Nageshwar Reddy
keywords: ABCG, 8 ATP-binding cassette, sub-family G (WHITE), member 8; ABCG6, ATP-binding cassette protein subfamily G, member 6; DNA, deoxyribose nucleic acid; GSD, gallstone disease; HDL, high density lipoprotein; LDL, low density lipoprotein; OR, odds ratio; PXR, pregnane C receptor; SD, standard deviation; SNPs, single nucleotide polymorphisms; UGT1A1 gene; UGT1A1, UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1); bilirubin; cholesterol gall stones; pigmentous gall stones; polymorphisms