Molecular phenotype of CXCL12beta 3'UTR G801A polymorphism (rs1801157) associated to HIV-1 disease progression.
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.
Garcia-Moruja
Carelia
C
Immunogenetics Unit and Human Molecular Pathology Unit, Experimental Biology Department, University of Jaén, Jaén, Spain.
Rueda
Patricia
P
Torres
Carmen
C
Alcamí
José
J
Luque
Francisco
F
Caruz
Antonio
A
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
D020413:3' Untranslated Regions; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D008156:Luciferases