title: Common genetic variation and haplotypes of the anion exchanger SLC4A2 in primary biliary cirrhosis.
abstract: OBJECTIVE
  Deficiencies of the anion exchanger SLC4A2 are thought to play a pathogenic role in primary biliary cirrhosis (PBC), as the evidenced by decreased expression and activity in PBC patients and development of disease features in SLC4A2 knockout mice. We hypothesized that genetic variation in SLC4A2 might influence this pathogenic contribution. Thus, we aimed to perform a comprehensive assessment of SLC4A2 genetic variation in PBC using a linkage disequilibrium (LD)-based haplotype-tagging approach.
  
  
  METHODS
  Twelve single nucleotide polymorphisms (SNPs) across SLC4A2 were genotyped in 409 PBC patients and 300 controls and evaluated for association with disease, as well as with prior orthotopic liver transplant and antimitochondrial antibody (AMA) status among the PBC patients, both individually and as inferred haplotypes, using logistic regression.
  
  
  RESULTS
  All SNPs were in Hardy-Weinberg equilibrium. No associations with disease or liver transplantation were detected, but two variants, rs2303929 and rs3793336, were associated with negativity for antimitochondrial antibodies among the PBC patients.
  
  
  CONCLUSIONS
  The common genetic variation of SLC4A2 does not directly affect the risk of PBC or its clinical outcome. Whether the deficiency of SLC4A2 expression and activity observed earlier in PBC patients is an acquired epiphenomenon of underlying disease or is because of heritable factors in unappreciated regulatory regions remains uncertain. Of note, two SLC4A2 variants appear to influence AMA status among PBC patients. The mechanisms behind this finding are unclear.
authors.affiliation: Division of Gastroenterology and Hepatology, Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Juran
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Atkinson
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Larson
authors.forename: Erik M
authors.initials: EM
authors.lastname: Schlicht
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Lazaridis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027321:Anion Transport Proteins / Q000097:blood / Q000235:genetics*; D017920:Antiporters / Q000097:blood / Q000235:genetics*; D001323:Autoantibodies / Q000276:immunology; D027963:Chloride-Bicarbonate Antiporters; D004247:DNA / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012307:Risk Factors; D064606:SLC4A Proteins
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D001323:Autoantibodies; D027963:Chloride-Bicarbonate Antiporters; D009419:Nerve Tissue Proteins; D064606:SLC4A Proteins; C579496:SLC4A2 protein, human; C579495:Slc4a2 protein, mouse; D004247:DNA