title: Hepatic cholesterol transporter ABCG8 polymorphisms in gallstone disease in an Indian population.
abstract: OBJECTIVE
  Gallstone formation is characterized by the abnormal regulation of cholesterol trafficking and solubilization. The prevalence of gallstone disease (GSD) differs between ethnic groups sharing the common environment. These differences can be explained by a genetic predisposition to gallstone formation. Studies have identified single nucleotide polymorphisms (SNP) D19H and T400K in the cholesterol transporter gene ATP-binding cassette, subfamily G, member 8 (ABCG8) in patients with cholesterol gallstones. The aim of this study was to analyze the relationship between D19H and T400K polymorphisms in the ABCG8 gene and GSD in an Indian population, and the effects of these polymorphisms on cholesterol levels in sera and bile.
  
  
  METHODS
  A total of 226 patients with GSD were analyzed for their lipid profile in plasma and bile. A total of 289 controls were recruited, and their plasma lipid profile was analyzed by standard protocols. The genotype of SNP D19H and T400K of ABCG8 was analyzed in 226 patients and 222 control samples. SNP D19H was analyzed by direct sequencing, and SNP T400K genotyping was assayed by the amplification refractory mutation system-polymerase chain reaction.
  
  
  RESULTS
  There was no significant difference in the allelic distribution of SNP T400K between the GSD and gallstone-free groups (P > 0.05), but the distribution of the SNP variant, D19H, was significantly higher (P = 0.017, odds ratio = 2.274) in patients compared to controls. The analysis of serum and bile cholesterol followed a strong association with genotypes.
  
  
  CONCLUSIONS
  SNP D19H, but not SNP T400K, in the ABCG8 gene is significantly associated with GSD in an Indian population.
authors.affiliation: Department of Basic Sciences, Asian Healthcare Foundation, Institute of Basic Sciences, Asian Institute of Gastroenterology, Hyderabad, Andhra Pradesh, India.
authors.forename: Siva Prasad
authors.initials: SP
authors.lastname: Siddapuram
authors.forename: Swapna
authors.initials: S
authors.lastname: Mahurkar
authors.forename: Nageshwar Reddy
authors.initials: NR
authors.lastname: Duvvuru
authors.forename: Sasikala
authors.initials: S
authors.lastname: Mitnala
authors.forename: Venkat Rao
authors.initials: VR
authors.lastname: Guduru
authors.forename: Pradeep
authors.initials: P
authors.lastname: Rebala
authors.forename: Magnus Jayaraj
authors.initials: MJ
authors.lastname: Mansard
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000483:Alleles; D001646:Bile / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D016001:Confidence Intervals; D004247:DNA / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005260:Female; D042882:Gallstones / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015995:Prevalence; D011379:Prognosis
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D004247:DNA; D002784:Cholesterol