Molecular Phenotype of CXCL12β 3UTR G801A Polymorphism (rs1801157) Associated to HIV-1 Disease Progression

Carelia      Garcia-Moruja; Patricia      Rueda; Carmen      Torres; Jose      Alcami; Francisco      Luque; Antonio      Caruz

Abstract

Objective: To investigate the molecular phenotype of the AIDS-onset delaying polymorphism in CXCL12β 3UTR (rs1801157). Methods: The 3UTRs of the CXCL12β 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 3A genotype compared to 3G 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 3A variant have two-fold longer half-life compared to the 3G variant (p = 6,99E-7). Conclusions: CXCL12β 3A 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.

Keywords: CXCL12, mRNA stability, AIDS, rs1801157, UTR

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