TY - JOUR
T1 - Molecular phenotype of CXCL12β 3'UTR G801A polymorphism (rs1801157) associated to HIV-1 disease progression
AU - Garcia-Moruja, Carelia
AU - Rueda, Patricia
AU - Torres, Carmen
AU - Alcamí, José
AU - Luque, Francisco
AU - Caruz, Antonio
PY - 2009/7
Y1 - 2009/7
N2 - Objective: To investigate the molecular phenotype of the AIDS-onset delaying polymorphism in CXCL12β 3'UTR (rs1801157). Methods: The 3'UTRs 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 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: CXCL12β3'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.
AB - Objective: To investigate the molecular phenotype of the AIDS-onset delaying polymorphism in CXCL12β 3'UTR (rs1801157). Methods: The 3'UTRs 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 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: CXCL12β3'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.
KW - AIDS
KW - CXCL12
KW - mRNA stability
KW - rs1801157
KW - UTR
UR - http://www.scopus.com/inward/record.url?scp=69849107435&partnerID=8YFLogxK
U2 - 10.2174/157016209788680543
DO - 10.2174/157016209788680543
M3 - Article
C2 - 19601773
AN - SCOPUS:69849107435
SN - 1570-162X
VL - 7
SP - 384
EP - 389
JO - Current HIV Research
JF - Current HIV Research
IS - 4
ER -