A genetic polymorphism of matrix metalloproteinase 9 (MMP-9) affects the changes in circulating MMP-9 levels induced by highly active antiretroviral therapy in HIV patients.
We examined whether two functional polymorphisms (g.-1562C>T and g.-90(CA)14-24) in the matrix metalloproteinase (MMP)-9 gene or MMP-9 haplotypes affect the circulating levels of pro-MMP-9 and pro-MMP-9/TIMP-1 (tissue inhibitor of metalloproteinase-1) ratios in AIDS patients, and modulate alterations in these biomarkers after highly active antiretroviral therapy (HAART). We studied 82 patients commencing HAART. Higher pro-MMP-9 concentrations and pro-MMP-9/TIMP-1 ratios were found in CT/TT patients compared with CC patients. HAART decreased pro-MMP-9 levels and pro-MMP-9/TIMP-1 ratios in CT/TT patients, it did not modify pro-MMP-9 levels and it increased pro-MMP-9/TIMP-1 ratios in CC patients. The g.-90(CA)14-24 polymorphism, however, produced no significant effects. Moreover, we found no significant differences in HAART-induced changes in plasma pro-MMP-9, TIMP-1 and pro-MMP-9/TIMP-1 ratios when different MMP-9 haplotypes were compared. These findings suggest that the g.-1562C>T polymorphism affects pro-MMP-9 levels in patients with AIDS and modulates the alterations in pro-MMP-9 levels caused by HAART, thus possibly affecting the risk of cardiovascular complications.
Demacq
C
C
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, Ribeirao Preto, SP, Brazil.
Vasconcellos
V B
VB
Marcaccini
A M
AM
Gerlach
R F
RF
Machado
A A
AA
Tanus-Santos
J E
JE
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000139:chemically induced; D004792:Enzyme Precursors; D005787:Gene Frequency; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D004792:Enzyme Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; C120487:pro-matrix metalloproteinase 9; D020780:Matrix Metalloproteinase 9