title: Molecular phenotype of CXCL12beta 3'UTR G801A polymorphism (rs1801157) associated to HIV-1 disease progression.
abstract: OBJECTIVE
  To investigate the molecular phenotype of the AIDS-onset delaying polymorphism in CXCL12beta 3'UTR (rs1801157).
  
  
  METHODS
  The 3 UTRs of the CXCL12beta isoform containing the A or G polymorphic variants were cloned downstream of the Luciferase gene under the control of the CXCL12 promoter. The plasmids were transfected in U373 and LC5 cells and the polymorphism phenotype was evaluated in terms of Luciferase activity and mRNA stability.
  
  
  RESULTS
  The 3'A genotype compared to 3'G leads to an increased luciferase activity in unstimulated and PMA+Ionomycin treated cells both in astrocytes (p = 0,0002, p = 0,02) and fibroblasts (p = 0,002, p = 0,03). The mRNA containing the 3'A variant have two-fold longer half-life compared to the 3'G variant (p = 6,99E(-7)).
  
  
  CONCLUSIONS
  CXCL12beta 3'A polymorphism, previously associated with resistance to AIDS progression and other diseases, leads to increased levels of CXCL12 mRNA, the results presented here demonstrate that this effect is a consequence of an enhanced mRNA stability. Our data contribute to characterize the CXCL12 as a potential pharmacological target in AIDS, autoimmune diseases and cancer.
authors: Immunogenetics Unit and Human Molecular Pathology Unit, Experimental Biology Department, University of Jaén, Jaén, Spain.
authors: Carelia
authors: C
authors: Garcia-Moruja
authors: Patricia
authors: P
authors: Rueda
authors: Carmen
authors: C
authors: Torres
authors: José
authors: J
authors: Alcamí
authors: Francisco
authors: F
authors: Luque
authors: Antonio
authors: A
authors: Caruz
mesh_terms: D020413:3' Untranslated Regions; D019677:Artificial Gene Fusion; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000235:genetics*; D003001:Cloning, Molecular; D017930:Genes, Reporter; D006678:HIV / Q000235:genetics*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D010957:Plasmids; D017354:Point Mutation; D011110:Polymorphism, Genetic; D020871:RNA Stability; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008156:Luciferases