title: Melanocortin-3-receptor promoter polymorphism associated with tuberculosis susceptibility does not influence protein expression.
abstract: BACKGROUND
  The melanocortin-3-receptor (MC3R) is a member of the G-protein coupled receptor family that mediate cellular response through the cyclic adenosine monophosphate signalling pathway. In the promoter region of MC3R the polymorphism rs6127698 has previously been shown to be strongly associated with tuberculosis susceptibility. It is predicted to generate an alternative transcription factor binding site.
  
  
  RESULTS
  We investigated the functional impact of rs6127698 by luciferase assay to assess if this polymorphism is capable of altering protein expression. Our results did not show any significant protein expression changes when comparing the two alleles of rs6127698.
  
  
  CONCLUSIONS
  Our experiments demonstrate that the rs6127698 polymorphism does not influence protein translation. A functional role of the predicted alternative transcription factor binding site could therefore not be confirmed. These results suggest rs6127698 has no direct role in tuberculosis susceptibility. The possibility remains that this polymorphism is linked to an adjacent functional genetic variant, acting as a surrogate marker for disease risk.
authors.affiliation: Institute of Human Genetics, University Hospital, Ludwig-Maximilians-University Munich, Munich, Germany. Marlene.Eggert@med.uni-muenchen.de
authors.forename: Marlene
authors.initials: M
authors.lastname: Eggert
authors.forename: Martina
authors.initials: M
authors.lastname: Pfob
authors.forename: Ortrud K
authors.initials: OK
authors.lastname: Steinlein
mesh_terms: D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044104:Receptor, Melanocortin, Type 3 / Q000235:genetics* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics*
chemical_list: D044104:Receptor, Melanocortin, Type 3