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

• Published in: The pharmacogenomics journal Vol. 9; no. 4; pp. 265 - 273
• Main Authors: Demacq, C, Vasconcellos, V B, Marcaccini, A M, Gerlach, R F, Machado, A A, Tanus-Santos, J E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2009; Nature Publishing Group
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - drug therapy; AIDS; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - adverse effects; Antiviral agents; Biomedical and Life Sciences; Biomedicine; Cardiovascular diseases; Cardiovascular Diseases - chemically induced; Dosage and administration; Drug therapy; Enzyme Precursors; Gelatinase B; Gene Expression; Gene Frequency; Gene polymorphism; Genetic aspects; Haplotypes; Highly active antiretroviral therapy; HIV; HIV infection; Human Genetics; Human immunodeficiency virus; Humans; Matrix metalloproteinase; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - genetics; Metalloenzymes; Metalloproteinase; Oncology; original-article; Pharmacogenetics; Pharmacotherapy; Physiological aspects; Polymorphism; Polymorphism, Genetic; Psychopharmacology; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - blood; Brazil; AIDS; polymorphism; MMP-9; pharmacogenetics; HAART
• DOI: 10.1038/tpj.2009.13
• ISSN: 1470-269X; 1473-1150

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.